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1.
J Cardiothorac Surg ; 19(1): 210, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38616244

RESUMO

Bilateral isolated common iliac artery aneurysms (CIAAs) are rare, and endovascular repair of CIAAs has emerged as an alternative to traditional open surgical repair. The primary goal of therapy is to exclude the aneurysm sac while maintaining perfusion of at least one internal iliac artery (IIA) to prevent pelvic ischemia. Although the iliac branch device (IBD) has improved the feasibility of preserving the IIA, its applicability is limited to a specific subset of aneurysm anatomy. We present a case series of three patients with bilateral isolated CIAAs in whom preoperative CT scans revealed an absence of a landing zone, the diameter of proximal CIA diameter was less than 13.0 mm, and normal diameter of the nonaneurysmal infrarenal aorta, making it challenging to use an IBD alone or a standard bifurcated aortic endograft to provide a proximal landing zone for iliac artery stenting. To overcome the small diameter of the infrarenal aorta, we implanted an aortic bifurcated unibody endograft. Then, we utilized a balloon-expandable covered stent-graft with overdilation as a modified sandwich technique to create an "eye of the tiger" configuration to prevent gutter leakage. The final angiography performed during the procedure revealed successful exclusion of the aneurysms, with blood flow to the right IIA and no type III endoleak. During the postoperative follow-up period, no patients exhibited symptoms associated with pelvic ischemia. There were no endoleaks or sac expansions on the two-year follow-up CT scans, and all external and internal iliac graft limbs were patent. This study demonstrated that a combination of an aortic bifurcated unibody endograft and a modified sandwich technique can effectively treat bilateral isolated CIAAs with certain anatomical constraints.


Assuntos
Procedimentos Endovasculares , Aneurisma Ilíaco , Humanos , Artéria Ilíaca , Aneurisma Ilíaco/cirurgia , Angiografia , Endoleak , Isquemia
2.
Zhongguo Zhong Yao Za Zhi ; 49(6): 1602-1610, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38621945

RESUMO

This study explored the mechanism of the ultrafiltration extract of Angelicae Sinensis Radix and Hedysari Radix in ameliorating renal fibrosis in the rat model of diabetic kidney disease(DKD) based on the expression of hypoxia-inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF) and HIF-1α/platelet-derived growth factor(PDGF)/platelet-derived growth factor receptor(PDGFR) signaling pathways in the DKD rats. After 1 week of adaptive feeding, 50 male SPF-grade Wistar rats were randomized into a blank group(n=7) and a modeling group. After 24 h of fasting, the rats in the modeling group were subjected to intraperitoneal injection of streptozocin and fed with a high-sugar and high-fat diet to establish a DKD model. After modeling, the rats were randomly assigned into model(n=7), low-dose ultrafiltration extract(n=7), medium-dose ultrafiltration extract(n=7), irbesartan(n=8), and high-dose ultrafiltration extract(n=8) groups. After intervention by corresponding drugs for 12 weeks, the general conditions of the rats were observed. The body weights and blood glucose levels of the rats were measured weekly, and the 24 h urinary protein(24hUP) was measured at the 6th and 12th weeks of drug administration. After the last drug administration, the renal function indicators were determined. Masson staining was employed to observe the pathological changes of the renal tissue. The expression of prolyl hydroxylase domain 2(PHD2) and HIF-1α in the renal tissue was detected by immunohistochemistry(IHC). Real-time qPCR was employed to determine the mRNA levels of PHD2, VEGF, PDGF, and PDGFR in the renal tissue. Western blot was employed to determine the protein levels of HIF-1α, VEGF, PDGF, and PDGFR in the renal tissue. The results showed that compared with the model group, drug administration lowered the levels of glycosylated serum protein(GSP), aerum creatinine(Scr), and blood urea nitrogen(BUN) in a dose-dependent manner(P<0.05 or P<0.01) and mitigated the pathological changes in the renal tissue. Furthermore, drug administration up-regulated mRNA level of PHD2(P<0.05 or P<0.01), down-regulated the mRNA levels of VEGF, PDGF, and PDGFR(P<0.05 or P<0.01) and the protein levels of HIF-1α, VEGF, PDGF, and PDGFR(P<0.01) in the renal tissue, and increased the rate of PHD2-positive cells(P<0.01). In conclusion, the ultrafiltration extract of Angelicae Sinensis Radix and Hedysari Radix effectively alleviated the renal fibrosis in DKD rats by inhibiting the expression of key proteins in the HIF-1α signaling pathway mediated by renal hypoxia and reducing extracellular matrix(ECM) deposition.


Assuntos
Nefropatias Diabéticas , Fator A de Crescimento do Endotélio Vascular , Ratos , Masculino , Animais , Ratos Wistar , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ultrafiltração , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Isquemia , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/genética , Fibrose , Hipóxia , Transdução de Sinais , RNA Mensageiro/metabolismo
3.
BMC Genomics ; 25(1): 367, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622534

RESUMO

The tissue damage caused by transient ischemic injury is an essential component of the pathogenesis of retinal ischemia, which mainly hinges on the degree and duration of interruption of the blood supply and the subsequent damage caused by tissue reperfusion. Some research indicated that the retinal injury induced by ischemia-reperfusion (I/R) was related to reperfusion time.In this study, we screened the differentially expressed circRNAs, lncRNAs, and mRNAs between the control and model group and at different reperfusion time (24h, 72h, and 7d) with the aid of whole transcriptome sequencing technology, and the trend changes in time-varying mRNA, lncRNA, circRNA were obtained by chronological analysis. Then, candidate circRNAs, lncRNAs, and mRNAs were obtained as the intersection of differentially expression genes and trend change genes. Importance scores of the genes selected the key genes whose expression changed with the increase of reperfusion time. Also, the characteristic differentially expressed genes specific to the reperfusion time were analyzed, key genes specific to reperfusion time were selected to show the change in biological process with the increase of reperfusion time.As a result, 316 candidate mRNAs, 137 candidate lncRNAs, and 31 candidate circRNAs were obtained by the intersection of differentially expressed mRNAs, lncRNAs, and circRNAs with trend mRNAs, trend lncRNAs and trend circRNAs, 5 key genes (Cd74, RT1-Da, RT1-CE5, RT1-Bb, RT1-DOa) were selected by importance scores of the genes. The result of GSEA showed that key genes were found to play vital roles in antigen processing and presentation, regulation of the actin cytoskeleton, and the ribosome. A network included 4 key genes (Cd74, RT1-Da, RT1-Bb, RT1-DOa), 34 miRNAs and 48 lncRNAs, and 81 regulatory relationship axes, and a network included 4 key genes (Cd74, RT1-Da, RT1-Bb, RT1-DOa), 9 miRNAs and 3 circRNAs (circRNA_10572, circRNA_03219, circRNA_11359) and 12 regulatory relationship axes were constructed, the subcellular location, transcription factors, signaling network, targeted drugs and relationship to eye diseases of key genes were predicted. 1370 characteristic differentially expressed mRNAs (spec_24h mRNA), 558 characteristic differentially expressed mRNAs (spec_72h mRNA), and 92 characteristic differentially expressed mRNAs (spec_7d mRNA) were found, and their key genes and regulation networks were analyzed.In summary, we screened the differentially expressed circRNAs, lncRNAs, and mRNAs between the control and model groups and at different reperfusion time (24h, 72h, and 7d). 5 key genes, Cd74, RT1-Da, RT1-CE5, RT1-Bb, RT1-DOa, were selected. Key genes specific to reperfusion time were selected to show the change in biological process with the increased reperfusion time. These results provided theoretical support and a reference basis for the clinical treatment.


Assuntos
MicroRNAs , RNA Longo não Codificante , Traumatismo por Reperfusão , Ratos , Animais , RNA Circular/genética , RNA Longo não Codificante/genética , MicroRNAs/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcriptoma , Traumatismo por Reperfusão/genética , Biologia Computacional/métodos , Isquemia , Redes Reguladoras de Genes
4.
Fluids Barriers CNS ; 21(1): 35, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622710

RESUMO

Early breach of the blood-brain barrier (BBB) and consequently extravasation of blood-borne substances into the brain parenchyma is a common hallmark of ischemic stroke. Although BBB breakdown is associated with an increased risk of cerebral hemorrhage and poor clinical prognosis, the cause and mechanism of this process are largely unknown. The aim of this study was to establish an imaging and analysis protocol which enables investigation of the dynamics of BBB breach in relation to hemodynamic properties along the arteriovenous axis. Using longitudinal intravital two-photon imaging following photothrombotic induction of ischemic stroke through a cranial window, we were able to study the response of the cerebral vasculature to ischemia, from the early critical hours to the days/weeks after the infarct. We demonstrate that disruption of the BBB and hemodynamic parameters, including perturbed blood flow, can be studied at single-vessel resolution in the three-dimensional space as early as 30 min after vessel occlusion. Further, we show that this protocol permits longitudinal studies on the response of individual blood vessels to ischemia over time, thus enabling detection of (maladaptive) vascular remodeling such as intussusception, angiogenic sprouting and entanglement of vessel networks. Taken together, this in vivo two-photon imaging and analysis protocol will be useful in future studies investigating the molecular and cellular mechanisms, and the spatial contribution, of BBB breach to disease progression which might ultimately aid the development of new and more precise treatment strategies for ischemic stroke.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Barreira Hematoencefálica/metabolismo , Acidente Vascular Cerebral/metabolismo , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/metabolismo , Isquemia/metabolismo
5.
BMC Cardiovasc Disord ; 24(1): 209, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627625

RESUMO

AIMS: Regular transient limb ischemia (RTLI) can prevent atherosclerosis (AS) progression in hypercholesterolemic rabbits. This study aimed to investigate the minimum effective intensity and possible mechanisms of RTLI for preventing atherosclerosis. METHODS: Eighty rabbits were divided into eight groups: normal (N), high cholesterol (H), three RTLI [three RTLI cycles every other day (R3qod), three RTLI cycles daily (R3qd), and six RTLI cycles daily (R6qd), each cycle of RTLI included 5 min of limb ischemia followed by 5 min limb reperfusion], and three correlated sham RTLI [sham ischemia for 30 min once every other day (S3qod), sham ischemia for 30 min once daily (S3qd), and sham ischemia for 60 min once daily (S6qd)]. Rabbits in group N were kept normally, while the others were fed 1% cholesterol diet for 12 weeks. The RTLI and sham RTLI groups were received RTLI or sham RTLI procedure, respectively. The plaque area in the thoracic aorta was determined by oil red O staining, and quantifying the ratio of plaque area to intimal area (PA/IA). Endothelium-dependent and -independent relaxation were also determined. Endothelial cell were isolated from abdominal aorta of rabbits, and the apoptosis ratio was detected using flow cytometry. RESULTS: The PA/IA and early apoptotic cell ratio was significantly lower as well as the endothelium-dependent relaxation response was higher in group R6qd than those in groups H and S6qd, while those in the R3qod group was not significantly different from those in groups H and S3qod, as well as those in the R3qd group showed no significant difference compared to those in groups H and S3qd. CONCLUSIONS: Six cycles of RTLI daily was the optimal effective intensity to prevent AS progression in rabbits. Endothelial function improvement and apoptosis inhibition might contribute to the anti-AS effects.


Assuntos
Aterosclerose , Animais , Coelhos , Aterosclerose/prevenção & controle , Aterosclerose/metabolismo , Colesterol/metabolismo , Apoptose , Isquemia/prevenção & controle , Células Endoteliais , Endotélio , Endotélio Vascular/metabolismo
6.
Acta Cir Bras ; 39: e391724, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38629650

RESUMO

PURPOSE: To investigate inflammation and cell adhesion molecules in the vagina after ovarian ischemia-reperfusion (IR) injury. METHODS: 20 Wistar albino female rats were divided into two groups: control, and IR groups. In IR group, blood flow was restricted for 2 hours for ovarian ischemia. Then, tissues were re-blood 2 hours for reperfusion. Vagina tissues were excised and processed for histopathological analysis. Histopathological and biochemical follow-ups were performed. RESULTS: Both malondialdehyde and myeloperoxidase values were increased in IR group compared to control group. Glutathione content was decreased in IR group compared to control group. Epithelial degeneration, inflammation, dilatation, and nuclear factor-κB (NF-κB) expression were increased in IR group compared to control group. E-cadherin expression was significantly decreased in IR group. In the IR group, E-cadherin showed a positive reaction in adenomas, gland-like cryptic structures, cellular junctions with clustered inflammatory cells. In the IR group, NF-κB expression was increased in basement membrane, inflammatory cells, in blood vessels. CONCLUSIONS: Ovarian ischemia caused degeneration of epithelial cells in the vaginal region and disruptions in the cell junction complex, which leads to activation of E-cadherin and NF-κB signaling pathway and alterations in reproductive and embryonal development in the vaginal region.


Assuntos
NF-kappa B , Traumatismo por Reperfusão , Ratos , Animais , Feminino , NF-kappa B/metabolismo , Ratos Wistar , Isquemia/metabolismo , Traumatismo por Reperfusão/patologia , Inflamação , Reperfusão , Caderinas
7.
Ren Fail ; 46(1): 2338565, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38622926

RESUMO

Background: Renal hypoxia plays a key role in the progression of chronic kidney disease (CKD). Shen Shuai II Recipe (SSR) has shown good results in the treatment of CKD as a common herbal formula. This study aimed to explore the effect of SSR on renal hypoxia and injury in CKD rats. Methods: Twenty-five Wistar rats underwent 5/6 renal ablation/infarction (A/I) surgery were randomly divided into three groups: 5/6 (A/I), 5/6 (A/I) + losartan (LOS), and 5/6 (A/I) + SSR groups. Another eight normal rats were used as the Sham group. After 8-week corresponding interventions, blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) was performed to evaluate renal oxygenation in all rats, and biochemical indicators were used to measure kidney and liver function, hemoglobin, and proteinuria. The expression of fibrosis and hypoxia-related proteins was analyzed using immunoblotting examination. Results: Renal oxygenation, evaluated by BOLD-fMRI as cortical and medullary T2* values (COT2* and MET2*), was decreased in 5/6 (A/I) rats, but increased after SSR treatment. SSR also downregulated the expression of hypoxia-inducible factor-1α (HIF-1α) in 5/6 (A/I) kidneys. With the improvement of renal hypoxia, renal function and fibrosis were improved in 5/6 (A/I) rats, accompanied by reduced proteinuria. Furthermore, the COT2* and MET2* were significantly positively correlated with the levels of creatinine clearance rate (Ccr) and hemoglobin, but negatively associated with the levels of serum creatinine (SCr), blood urea nitrogen (BUN), serum cystatin C (CysC), serum uric acid (UA), 24-h urinary protein (24-h Upr), and urinary albumin:creatinine ratio (UACR). Conclusion: The degree of renal oxygenation reduction is correlated with the severity of renal injury in CKD. SSR can improve renal hypoxia to attenuate renal injury in 5/6 (A/I) rats of CKD.


Assuntos
Insuficiência Renal Crônica , Ácido Úrico , Ratos , Animais , Creatinina/metabolismo , Ácido Úrico/farmacologia , Ratos Sprague-Dawley , Ratos Wistar , Rim , Isquemia , Infarto/metabolismo , Infarto/patologia , Hipóxia/tratamento farmacológico , Hipóxia/metabolismo , Hipóxia/patologia , Fibrose , Proteinúria/patologia , Imageamento por Ressonância Magnética/métodos , Hemoglobinas/metabolismo
8.
J Neurosci Res ; 102(4): e25329, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38597144

RESUMO

There is a need for new treatments to reduce brain injuries derived from neonatal hypoxia/ischemia. The only viable option used in the clinic today in infants born at term is therapeutic hypothermia, which has a limited efficacy. Treatments with exogenous RNase have shown great promise in a range of different adult animal models including stroke, ischemia/reperfusion injury, or experimental heart transplantation, often by conferring vascular protective and anti-inflammatory effects. However, any neuroprotective function of RNase treatment in the neonate remains unknown. Using a well-established model of neonatal hypoxic/ischemic brain injury, we evaluated the influence of RNase treatment on RNase activity, gray and white matter tissue loss, blood-brain barrier function, as well as levels and expression of inflammatory cytokines in the brain up to 6 h after the injury using multiplex immunoassay and RT-PCR. Intraperitoneal treatment with RNase increased RNase activity in both plasma and cerebropinal fluids. The RNase treatment resulted in a reduction of brain tissue loss but did not affect the blood-brain barrier function and had only a minor modulatory effect on the inflammatory response. It is concluded that RNase treatment may be promising as a neuroprotective regimen, whereas the mechanistic effects of this treatment appear to be different in the neonate compared to the adult and need further investigation.


Assuntos
Lesões Encefálicas , Hipóxia-Isquemia Encefálica , Fármacos Neuroprotetores , Animais , Recém-Nascido , Lactente , Humanos , Animais Recém-Nascidos , Ribonucleases/metabolismo , Ribonucleases/farmacologia , Lesões Encefálicas/tratamento farmacológico , Encéfalo/metabolismo , Isquemia/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Modelos Animais de Doenças
9.
Arq Bras Cardiol ; 121(2): e20230540, 2024.
Artigo em Português, Inglês | MEDLINE | ID: mdl-38597536

RESUMO

BACKGROUND: Ischemia with the non-obstructive coronary artery (INOCA) is an ischemic heart disease that mostly includes coronary microvascular dysfunction and/or epicardial coronary vasospasm due to underlying coronary vascular dysfunction and can be seen more commonly in female patients. The systemic immune-inflammation index (SII, platelet × neutrophil/lymphocyte ratio) is a new marker that predicts adverse clinical outcomes in coronary artery disease (CAD). OBJECTIVE: This study aims to investigate the relationship between INOCA and SII, a new marker associated with inflammation. METHODS: A total of 424 patients (212 patients with INOCA and 212 normal controls) were included in the study. Peripheral venous blood samples were received from the entire study population prior to coronary angiography to measure SII and other hematological parameters. In our study, the value of p<0.05' was considered statistically significant. RESULTS: The optimal cut-off value of SII for predicting INOCA was 153.8 with a sensitivity of 44.8% and a specificity of 78.77% (Area under the curve [AUC]: 0.651 [95% CI: 0.603-0.696, p=0.0265]). Their ROC curves were compared to assess whether SII had an additional predictive value over components. The AUC value of SII was found to be significantly higher than that of lymphocyte (AUC: 0.607 [95% CI: 0.559-0.654, p = 0.0273]), neutrophil (AUC: 0.559 [95%CI: 0.511-0.607, p=0.028]) and platelet (AUC: 0.590 [95% CI: 0.541-0.637, p = 0.0276]) in INOCA patients. CONCLUSIONS: A high SII level was found to be independently associated with the existence of INOCA. The SII value can be used as an indicator to add to the traditional expensive methods commonly used in INOCA prediction.


FUNDAMENTO: A isquemia com artéria coronária não obstrutiva (INOCA) é uma doença cardíaca isquêmica que inclui principalmente disfunção microvascular coronariana e/ou vasoespasmo coronariano epicárdico devido à disfunção vascular coronariana subjacente e pode ser observada mais comumente em pacientes do sexo feminino. O índice de inflamação imunológica sistêmica (SII, relação plaquetas × neutrófilos/linfócitos) é um novo marcador que prediz resultados clínicos adversos na doença arterial coronariana (DAC). OBJETIVO: Este estudo tem como objetivo investigar a relação entre INOCA e SII, um novo marcador associado à inflamação. MÉTODOS: Um total de 424 pacientes (212 pacientes com INOCA e 212 controles normais) foram incluídos no estudo. Amostras de sangue venoso periférico foram recebidas de toda a população do estudo antes da angiografia coronária para medir o SII e outros parâmetros hematológicos. Em nosso estudo o valor de p<0,05' foi considerado estatisticamente significativo. RESULTADOS: O valor de corte ideal do SII para prever o INOCA foi 153,8, com sensibilidade de 44,8% e especificidade de 78,77% (Área sob a curva [AUC]: 0,651 [IC 95%: 0,603­0,696, p=0,0265]). Suas curvas ROC foram comparadas para avaliar se o SII tinha um efeito preditivo adicional valor sobre os componentes. O valor da AUC do SII foi significativamente maior do que o do linfócito (AUC: 0,607 [IC 95%: 0,559­0,654, p = 0,0273]), neutrófilos (AUC: 0,559 [IC 95%: 0,511­0,607, p = 0,028]) e plaquetas (AUC: 0,590 [IC 95%: 0,541­0,637, p = 0,0276]) em pacientes INOCA. CONCLUSÕES: Verificou-se que um nível elevado de SII estava independentemente associado à existência de INOCA. O valor do SII pode ser usado como um indicador para adicionar aos métodos tradicionais e caros comumente usados na previsão do INOCA.


Assuntos
Vasos Coronários , Isquemia Miocárdica , Humanos , Feminino , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Isquemia , Isquemia Miocárdica/diagnóstico por imagem , Inflamação/diagnóstico por imagem
10.
Arq Bras Cardiol ; 121(3): e20230049, 2024.
Artigo em Português, Inglês | MEDLINE | ID: mdl-38597551

RESUMO

BACKGROUND: The management of unstable angina (UA) presents a challenge due to its subjective diagnosis and limited representation in randomized clinical trials that inform current practices. OBJECTIVES: This study aims to identify key factors associated with the indication for invasive versus non-invasive stratification in this population and to evaluate factors associated with stratification test results. METHODS: This retrospective cohort study included patients hospitalized with UA over a consecutive 20-month period. To assess factors associated with stratification strategies, patients were divided into invasive stratification (coronary angiography) and non-invasive stratification (other methods) groups. For the analysis of factors related to changes in stratification tests, patients were categorized into groups with or without obstructive coronary artery disease (CAD) or ischemia, as per the results of the requested tests. Comparisons between groups and multiple logistic regression analyses were performed, with statistical significance set at a 5% level. RESULTS: A total of 729 patients were included, with a median age of 63 years and a predominance of males (64.6%). Factors associated with invasive stratification included smoking (p = 0.001); type of chest pain (p < 0.001); "crescendo" pain (p = 0.006); TIMI score (p = 0.006); HEART score (p = 0.011). In multivariate analysis, current smokers (OR 2.23, 95% CI 1.13-4.8), former smokers (OR 2.19, 95% CI 1.39-3.53), and type A chest pain (OR 3.39, 95% CI 1.93-6.66) were independently associated. Factors associated with obstructive CAD or ischemia included length of hospital stay (p < 0.001); male gender (p = 0.032); effort-induced pain (p = 0.037); Diamond-Forrester score (p = 0.026); TIMI score (p = 0.001). In multivariate analysis, only chest pain (type B chest pain: OR 0.6, 95% CI 0.38-0.93, p = 0.026) and previous CAD (OR 1.42, 95% CI 1.01-2.0, p = 0.048) were independently associated. CONCLUSION: The type of chest pain plays a crucial role not only in the diagnosis of UA but also in determining the appropriate treatment. Our results highlight the importance of incorporating pain characteristics into prognostic scores endorsed by guidelines to optimize UA management.


FUNDAMENTO: O manejo da angina instável (AI) é um desafio devido ao seu diagnóstico subjetivo e à sua escassa representação em ensaios clínicos randomizados que determinem as práticas atuais. OBJETIVOS: O objetivo deste estudo é identificar os principais fatores associados à indicação de estratificação invasiva ou não nessa população e avaliar os fatores associados às alterações nos exames de estratificação. MÉTODOS: Coorte retrospectiva de pacientes internados por AI, em um período de 20 meses consecutivos. Para avaliar os fatores associados à estratégia de estratificação, os pacientes foram divididos em estratificação invasiva (cinecoronariografia) e não invasiva (demais métodos). Para análise de fatores relacionados às alterações nos exames de estratificação, os pacientes foram divididos em grupos com ou sem doença arterial coronariana (DAC) obstrutiva ou isquemia, conforme resultados dos exames solicitados. Foram realizadas comparações entre grupos e análise de regressão logística múltipla, com significância estatística definida em um nível de 5%. RESULTADOS: 729 pacientes foram incluídos, com mediana de idade de 63 anos e predomínio do sexo masculino (64,6%). Estiveram associados à estratificação invasiva: tabagismo (p = 0,001); tipo de dor torácica (p < 0,001); dor "em crescendo" (p = 0,006); escore TIMI (p = 0,006); escore HEART (p = 0,011). Na análise multivariada, tabagistas (OR 2,23, IC 95% 1,13-4,8), ex-tabagistas (OR 2,19, IC 1,39-3,53) e dor torácica tipo A (OR 3,39, IC 95% 1,93-6,66) estiveram associados de forma independente. Estiveram associados à DAC obstrutiva ou isquemia: tempo de internação hospitalar (p < 0,001); sexo masculino (p = 0,032); dor desencadeada por esforço (p = 0,037); Diamond-Forrester (p = 0,026); escore TIMI (p = 0,001). Na análise multivariada, apenas dor torácica (dor torácica tipo B: OR 0,6, IC 95% 0,38-0,93, p = 0,026) e DAC prévia (OR 1,42, IC 95% 1,01-2,0, p = 0,048) estiveram associadas de maneira independente. CONCLUSÕES: O tipo de dor torácica desempenha um papel crucial não apenas no diagnóstico da AI, mas também na definição do tratamento adequado. Nossos resultados destacam a importância de incorporar características da dor aos escores prognósticos endossados pelas diretrizes, para otimização do manejo da AI.


Assuntos
Cardiologia , Doença da Artéria Coronariana , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Fatores de Risco , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Angina Instável/diagnóstico , Dor no Peito/diagnóstico , Dor no Peito/etiologia , Angiografia Coronária/métodos , Isquemia/complicações , Serviço Hospitalar de Emergência , Medição de Risco/métodos , Valor Preditivo dos Testes
11.
Int J Mol Med ; 53(5)2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38577949

RESUMO

Several studies have shown that berberine (BBR) is effective in protecting against myocardial ischemia­reperfusion injury (MI/RI). However, the precise molecular mechanism remains elusive. The present study observed the mechanism and the safeguarding effect of BBR against hypoxia/reoxygenation (H/R) myocardial injury in H9c2 cells. BBR pretreatment significantly improved the decrease of cell viability, P62 protein, Rho Family GTPase 3 (RhoE) protein, ubiquinone subunit B8 protein, ubiquinol­cytochrome c reductase core protein U, the Bcl­2­associated X protein/B­cell lymphoma 2 ratio, glutathione (GSH) and the GSH/glutathione disulphide (GSSG) ratio induced by H/R, while reducing the increase in lactate dehydrogenase, microtubule­associated protein 1 light 3 protein, caspase­3 activity, reactive oxygen species, GSSG and malonaldehyde caused by H/R. Transmission electron microscopy and LysoTracker Red DND­99 staining results showed that BBR pretreatment inhibited H/R­induced excessive autophagy by mediating RhoE. BBR also inhibited mitochondrial permeability transition, maintained the stability of the mitochondrial membrane potential, reduced the apoptotic rate, and increased the level of caspase­3. However, the protective effects of BBR were attenuated by pAD/RhoE­small hairpin RNA, rapamycin (an autophagy activator) and compound C (an AMP­activated protein kinase inhibitor). These new findings suggested that BBR protects the myocardium from MI/RI by inhibiting excessive autophagy, maintaining mitochondrial function, improving the energy supply and redox homeostasis, and attenuating apoptosis through the RhoE/AMP­activated protein kinase pathway.


Assuntos
Proteínas Quinases Ativadas por AMP , Autofagia , Berberina , Traumatismo por Reperfusão Miocárdica , Proteínas Quinases Ativadas por AMP/metabolismo , Apoptose , Berberina/farmacologia , Caspase 3/metabolismo , Dissulfeto de Glutationa/metabolismo , Isquemia/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/etiologia , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Animais , Ratos
12.
Biol Direct ; 19(1): 26, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582839

RESUMO

Ischemic stroke is a sudden and acute disease characterized by neuronal death, increment of reactive gliosis (reactive microglia and astrocytes), and a severe inflammatory process. Neuroinflammation is an early event after cerebral ischemia, with microglia playing a leading role. Reactive microglia involve functional and morphological changes that drive a wide variety of phenotypes. In this context, deciphering the molecular mechanisms underlying such reactive microglial is essential to devise strategies to protect neurons and maintain certain brain functions affected by early neuroinflammation after ischemia. Here, we studied the role of mammalian target of rapamycin (mTOR) activity in the microglial response using a murine model of cerebral ischemia in the acute phase. We also determined the therapeutic relevance of the pharmacological administration of rapamycin, a mTOR inhibitor, before and after ischemic injury. Our data show that rapamycin, administered before or after brain ischemia induction, reduced the volume of brain damage and neuronal loss by attenuating the microglial response. Therefore, our findings indicate that the pharmacological inhibition of mTORC1 in the acute phase of ischemia may provide an alternative strategy to reduce neuronal damage through attenuation of the associated neuroinflammation.


Assuntos
Isquemia Encefálica , Microglia , Camundongos , Animais , Alvo Mecanístico do Complexo 1 de Rapamicina , Doenças Neuroinflamatórias , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/genética , Serina-Treonina Quinases TOR/uso terapêutico , Isquemia , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Mamíferos
13.
Sci Rep ; 14(1): 7924, 2024 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575644

RESUMO

Neonatal hypoxic-ischemic brain injury (HIBI) results in part from excess reactive oxygen species and iron-dependent lipid peroxidation (i.e. ferroptosis). The vitamin D precursor 7-dehydrocholesterol (7-DHC) may inhibit iron-dependent lipid peroxidation. Primary neurons underwent oxygen and glucose deprivation (OGD) injury and treatment with 7-DHC-elevating medications such as cariprazine (CAR) or vehicle. Postnatal day 9 mice underwent sham surgery or carotid artery ligation and hypoxia and received intraperitoneal CAR. In neurons, CAR administration resulted in significantly increased cell survival compared to vehicle controls, whether administered 48 h prior to or 30 min after OGD, and was associated with increased 7-DHC. In the mouse model, malondialdehyde and infarct area significantly increased after HIBI in the vehicle group, which were attenuated by post-treatment with CAR and were negatively correlated with tissue 7-DHC concentrations. Elevating 7-DHC concentrations with CAR was associated with improved cellular and tissue viability after hypoxic-ischemic injury, suggesting a novel therapeutic avenue.


Assuntos
Desidrocolesteróis , Ferroptose , Hipóxia-Isquemia Encefálica , Animais , Camundongos , Animais Recém-Nascidos , Encéfalo , Hipóxia/complicações , Oxigênio/uso terapêutico , Isquemia/complicações , Ferro/uso terapêutico
14.
J Cardiothorac Surg ; 19(1): 183, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580973

RESUMO

BACKGROUND: Acute type A aortic dissection (ATAAD) complicated by mesenteric malperfusion is a critical and complicated condition. The optimal treatment strategy remains controversial, debate exists as to whether aortic dissection or mesenteric malperfusion should be addressed first, and the exact time window for mesenteric ischemia intervention is still unclear. To solve this problem, we developed a new concept based on the pathophysiological mechanism of mesenteric ischemia, using a 6-hour time window to divide newly admitted patients by the time from onset to admission, applying different treatment protocols to improve the clinical outcomes of patients with ATAAD complicated by mesenteric malperfusion. METHODS: This was a retrospective study that covered a five-year period. From July 2018 to December 2020(phase I), all patients underwent emergency open surgery. From January 2021 to June 2023(phase II), patients with an onset within 6 h all underwent open surgical repair, followed by immediately postoperative examination if the malperfusion is suspected, while the restoration of mesenteric perfusion and visceral organ function was performed first, followed by open repair, in patients with an onset beyond 6 h. RESULTS: There were no significant differences in baseline and surgical data. In phase I, eleven patients with mesenteric malperfusion underwent open surgery, while in phase II, our novel strategy was applied, with sixteen patients with an onset greater than 6 h and eleven patients with an onset less than 6 h. During the waiting period, none died of aortic rupture, but four patients died of organ failure, twelve patients had organ function improvement and underwent surgery successfully survived. The overall mortality rate decreased with the use of this novel strategy (54.55% vs. 18.52%, p = 0.047). Furthermore, the surgical mortality rate between the two periods showed even stronger statistical significance (54.55% vs. 4.35%, p = 0.022). Moreover, the proportions of patients with sepsis and multiorgan failure also showed differences. CONCLUSIONS: Our novel strategy for patients with ATAAD complicated by mesenteric malperfusion not only improves the surgical success rate but also reduces the overall mortality rate.


Assuntos
Aneurisma Aórtico , Dissecção Aórtica , Procedimentos Endovasculares , Isquemia Mesentérica , Humanos , Aneurisma Aórtico/complicações , Aneurisma Aórtico/cirurgia , Aneurisma Aórtico/diagnóstico , Isquemia Mesentérica/cirurgia , Isquemia Mesentérica/etiologia , Isquemia/cirurgia , Isquemia/etiologia , Estudos Retrospectivos , Procedimentos Endovasculares/efeitos adversos , Doença Aguda , Resultado do Tratamento , Dissecção Aórtica/complicações , Dissecção Aórtica/cirurgia
15.
Int J Mol Sci ; 25(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38612582

RESUMO

Ischemic heart disease, a leading cause of death worldwide, manifests clinically as myocardial infarction. Contemporary therapies using mesenchymal stromal cells (MSCs) and their derivative (exosomes, EXOs) were developed to decrease the progression of cell damage during ischemic injury. Laminin alpha 2 (LAMA2) is an important extracellular matrix protein of the heart. Here, we generated MSC-derived exosomes cultivated under LAMA2 coating to enhance human-induced pluripotent stem cell (hiPSC)-cardiomyocyte recognition of LAMA2-EXOs, thus, increasing cell protection during ischemia reoxygenation. We mapped the mRNA content of LAMA2 and gelatin-EXOs and identified 798 genes that were differentially expressed, including genes associated with cardiac muscle development and extracellular matrix organization. Cells were treated with LAMA2-EXOs 2 h before a 4 h ischemia period (1% O2, 5% CO2, glucose-free media). LAMA2-EXOs had a two-fold protective effect compared to non-treatment on plasma membrane integrity and the apoptosis activation pathway; after a 1.5 h recovery period (20% O2, 5% CO2, cardiomyocyte-enriched media), cardiomyocytes treated with LAMA2-EXOs showed faster recovery than did the control group. Although EXOs had a protective effect on endothelial cells, there was no LAMA2-enhanced protection on these cells. This is the first report of LAMA2-EXOs used to treat cardiomyocytes that underwent ischemia-reoxygenation injury. Overall, we showed that membrane-specific EXOs may help improve cardiomyocyte survival in treating ischemic cardiovascular disease.


Assuntos
Exossomos , Células-Tronco Pluripotentes Induzidas , Laminina , Humanos , Miócitos Cardíacos , Dióxido de Carbono , Células Endoteliais , Isquemia
16.
Int J Mol Sci ; 25(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38612596

RESUMO

A better understanding of the function of neutrophil extracellular traps (NETs) may facilitate the development of interventions for sepsis. The study aims to investigate the formation and degradation of NETs in three murine sepsis models and to analyze the production of reactive oxygen species (ROS) during NET formation. Murine sepsis was induced by midgut volvulus (720° for 15 min), cecal ligation and puncture (CLP), or the application of lipopolysaccharide (LPS) (10 mg/kg body weight i.p.). NET formation and degradation was modulated using mice that were genetically deficient for peptidyl arginine deiminase-4 (PAD4-KO) or DNase1 and 1L3 (DNase1/1L3-DKO). After 48 h, mice were killed. Plasma levels of circulating free DNA (cfDNA) and neutrophil elastase (NE) were quantified to assess NET formation and degradation. Plasma deoxyribonuclease1 (DNase1) protein levels, as well as tissue malondialdehyde (MDA) activity and glutathione peroxidase (GPx) activity, were quantified. DNase1 and DNase1L3 in liver, intestine, spleen, and lung tissues were assessed. The applied sepsis models resulted in a simultaneous increase in NET formation and oxidative stress. NET formation and survival differed in the three models. In contrast to LPS and Volvulus, CLP-induced sepsis showed a decreased and increased 48 h survival in PAD4-KO and DNase1/1L3-DKO mice, when compared to WT mice, respectively. PAD4-KO mice showed decreased formation of NETs and ROS, while DNase1/1L3-DKO mice with impaired NET degradation accumulated ROS and chronicled the septic state. The findings indicate a dual role for NET formation and degradation in sepsis and ischemia-reperfusion (I/R) injury: NETs seem to exhibit a protective capacity in certain sepsis paradigms (CLP model), whereas, collectively, they seem to contribute adversely to scenarios where sepsis is combined with ischemia-reperfusion (volvulus).


Assuntos
Antígenos de Grupos Sanguíneos , Ácidos Nucleicos Livres , Armadilhas Extracelulares , Volvo Intestinal , Traumatismo por Reperfusão , Sepse , Animais , Camundongos , Modelos Animais de Doenças , Lipopolissacarídeos , Espécies Reativas de Oxigênio , Sepse/complicações , Prótons , Isquemia
17.
Int J Mol Sci ; 25(7)2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38612680

RESUMO

The central exacerbating factor in the pathophysiology of ischemic-reperfusion acute kidney injury (AKI) is oxidative stress. Lipid peroxidation and DNA damage in ischemia are accompanied by the formation of 3-nitrotyrosine, a biomarker for oxidative damage. DNA double-strand breaks (DSBs) may also be a result of postischemic AKI. γH2AX(S139) histone has been identified as a potentially useful biomarker of DNA DSBs. On the other hand, hypoxia-inducible factor (HIF) is the "master switch" for hypoxic adaptation in cells and tissues. The aim of this research was to evaluate the influence of hyperbaric oxygen (HBO) preconditioning on antioxidant capacity estimated by FRAP (ferric reducing antioxidant power) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) assay, as well as on oxidative stress parameter 3-nitrotyrosine, and to assess its effects on γH2AX(S139), HIF-1α, and nuclear factor-κB (NF-κB) expression, in an experimental model of postischemic AKI induced in spontaneously hypertensive rats. The animals were divided randomly into three experimental groups: sham-operated rats (SHAM, n = 6), rats with induced postischemic AKI (AKI, n = 6), and group exposed to HBO preconditioning before AKI induction (AKI + HBO, n = 6). A significant improvement in the estimated glomerular filtration rate, eGFR, in AKI + HBO group (p < 0.05 vs. AKI group) was accompanied with a significant increase in plasma antioxidant capacity estimated by FRAP (p < 0.05 vs. SHAM group) and a reduced immunohistochemical expression of 3-nitrotyrosine and γH2AX(S139). Also, HBO pretreatment significantly increased HIF-1α expression (p < 0.001 vs. AKI group), estimated by Western blot and immunohistochemical analysis in kidney tissue, and decreased immunohistochemical NF-κB renal expression (p < 0.01). Taking all of these results together, we may conclude that HBO preconditioning has beneficial effects on acute kidney injury induced in spontaneously hypertensive rats.


Assuntos
Injúria Renal Aguda , Oxigenoterapia Hiperbárica , Traumatismo por Reperfusão , Animais , Ratos , Antioxidantes , NF-kappa B , Ratos Endogâmicos SHR , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Rim , Isquemia , Reperfusão , Estresse Oxidativo , Oxigênio , Dano ao DNA , Biomarcadores , DNA
18.
Int J Mol Sci ; 25(7)2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38612835

RESUMO

Peripheral arterial disease (PAD) strikes more than 200 million people worldwide and has a severe prognosis by potentially leading to limb amputation and/or death, particularly in older patients. Skeletal muscle mitochondrial dysfunctions and oxidative stress play major roles in this disease in relation with ischemia-reperfusion (IR) cycles. Mitochondrial dynamics through impairment of fission-fusion balance may contribute to skeletal muscle pathophysiology, but no data were reported in the setting of lower-limb IR despite the need for new therapeutic options. We, therefore, investigated the potential protective effect of mitochondrial division inhibitor-1 (mDivi-1; 50 mg/kg) in young (23 weeks) and old (83 weeks) mice submitted to two-hour ischemia followed by two-hour reperfusion on systemic lactate, muscle mitochondrial respiration and calcium retention capacity, and on transcripts specific for oxidative stress and mitochondrial dynamics. At the systemic levels, an IR-related increase in circulating lactate was still major despite mDivi-1 use (+305.9% p < 0.0001, and +269.4% p < 0.0001 in young and old mice, respectively). Further, IR-induced skeletal muscle mitochondrial dysfunctions (more severely impaired mitochondrial respiration in old mice (OXPHOS CI state, -68.2% p < 0.0001 and -84.9% p < 0.0001 in 23- and 83-week mice) and reduced calcium retention capacity (-46.1% p < 0.001 and -48.2% p = 0.09, respectively) were not corrected by mDivi-1 preconditioning, whatever the age. Further, mDivi-1 treatment did not oppose superoxide anion production (+71.4% p < 0.0001 and +37.5% p < 0.05, respectively). At the transcript level, markers of antioxidant enzymes (SOD 1, SOD 2, catalase, and GPx) and fission markers (Drp1, Fis) remained unchanged or tended to be decreased in the ischemic leg. Fusion markers such as mitofusin 1 or 2 decreased significantly after IR in both groups. In conclusion, aging enhanced the deleterious effects or IR on muscle mitochondrial respiration, and in this setting of lower-limb IR, mDivi-1 failed to protect the skeletal muscle both in young and old mice.


Assuntos
Doenças Mitocondriais , Doença Arterial Periférica , Quinazolinonas , Humanos , Animais , Camundongos , Idoso , Dinâmica Mitocondrial , Cálcio , Isquemia/tratamento farmacológico , Músculo Esquelético , Ácido Láctico , Superóxido Dismutase
19.
Sci Prog ; 107(2): 368504241239444, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38614462

RESUMO

BACKGROUND: Ischemia-reperfusion injury (IRI) poses a significant challenge for physicians, necessitating the management of cell damage and the preservation of organ functions. Various surgical procedures, such as vascular surgery on extremities, temporary cross-clamping of the abdominal aorta in aortic surgery, and the use of a tourniquet in extremity surgeries, may induce lower limb IRI. The susceptibility to IRI is heightened in individuals with diabetes. This study aimed to investigate the effects of fullerenol C60 and sevoflurane on mouse muscle tissue in a lower limb IRI model and to assess their potential in preventing complications arising from ischemia-reperfusion in mice with streptozocin-induced diabetes. METHODS: A total of 36 adult Swiss albino mice were randomly divided into six groups, each consisting of six mice: control group (group C), diabetes group (group D), diabetes-ischemia/reperfusion group (group DIR), diabetes-ischemia/reperfusion-fullerenol C60 group (group DIR-FC60), diabetes-ischemia/reperfusion-sevoflurane group (group DIR-S), and diabetes-ischemia/reperfusion-sevoflurane-fullerenol C60 group (DIR-S-FC60). Streptozocin (55 mg/kg) was intraperitoneally administered to induce diabetes in the relevant groups, with mice displaying blood glucose levels of 250 mg/dL or higher at 72 h were considered diabetic. After 4 weeks, all groups underwent laparotomy under anesthesia. In DIR-FC60 and DIR-S-FC60 groups, fullerenol C60 (100 mg/kg) was intraperitoneally administrated 30 min before the ischemia period. Sevoflurane, delivered in 100% oxygen at a rate of 2.3% and 4 L/min, was administered during the ischemia period in DIR-S and DIR-S-FC60 groups. In the IR groups, a microvascular clamp was placed on the infrarenal abdominal aorta for 120 min during the ischemia period, followed by the removal of the clamp and a 120-min reperfusion period. At the end of the reperfusion, gastrocnemius muscle tissues were removed for histopathological and biochemical parameter examinations. RESULTS: Histopathological examination revealed a significant reduction in the disorganization and degeneration of muscle cells in the DIR-S-FC60 group compared to the DIR group (p = 0.041). Inflammatory cell infiltration was notably lower in the DIR-S, DIR-FC60, and DIR-S-FC60 groups than in the DIR group (p = 0.031, p = 0.011, and p = 0.013, respectively). The total damage scores in the DIR-FC60 and DIR-S-FC60 groups were significantly lower than in the DIR group (p = 0.018 and p = 0.008, respectively). Furthermore, the levels of malondialdehyde (MDA) in the DIR-S, DIR-FC60, and DIR-S-FC60 groups were significantly lower than in the DIR group (p < 0.001, p < 0.001, and p < 0.001, respectively). Catalase (CAT) enzyme activity in the DIR-S, DIR-FC60, and DIR-S-FC60 groups was higher than in the DIR group (p = 0.001, p = 0.014, and p < 0.001, respectively). Superoxide dismutase (SOD) enzyme activity in the DIR-FC60 and DIR-S-FC60 groups was also higher than in the DIR group (p < 0.001 and p = 0.001, respectively). CONCLUSION: Our findings indicate that administering fullerenol C60 30 min prior to ischemia in diabetic mice, in combination with sevoflurane, led to a reduction in oxidative stress and the correction of IR-related damage in muscle tissue histopathology. We believe that the administration of fullerenol C60 before IR, coupled with sevoflurane administration during IR, exerts a protective effect in mice.


Assuntos
Diabetes Mellitus Experimental , Fulerenos , Traumatismo por Reperfusão , Animais , Camundongos , Sevoflurano , Estreptozocina , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Isquemia , Traumatismo por Reperfusão/tratamento farmacológico , Extremidade Inferior
20.
Ren Fail ; 46(1): 2332492, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38584135

RESUMO

Acute kidney injury (AKI) is associated with a high mortality rate. Pathologically, renal ischemia/reperfusion injury (RIRI) is one of the primary causes of AKI, and hypoxia-inducible factor (HIF)-1α may play a defensive role in RIRI. This study assessed the role of hypoxia-inducible factor 1α (HIF-1α)-mediated mitophagy in protection against RIRI in vitro and in vivo. The human tubular cell line HK-2 was used to assess hypoxia/reoxygenation (H/R)-induced mitophagy through different in vitro assays, including western blotting, immunofluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and reactive oxygen species (ROS) measurement. Additionally, a rat RIRI model was established for evaluation by renal histopathology, renal Doppler ultrasound, and transmission electron microscopy to confirm the in vitro data. The selective HIF-1α inhibitor LW6 reduced H/R-induced mitophagy but increased H/R-induced apoptosis and ROS production. Moreover, H/R treatment enhanced expression of the FUN14 domain-containing 1 (FUNDC1) protein. Additionally, FUNDC1 overexpression reversed the effects of LW6 on the altered expression of light chain 3 (LC3) BII and voltage-dependent anion channels as well as blocked the effects of HIF-1α inhibition in cells. Pretreatment of the rat RIRI model with roxadustat, a novel oral HIF-1α inhibitor, led to decreased renal injury and apoptosis in vivo. In conclusion, the HIF-1α/FUNDC1 signaling pathway mediates H/R-promoted renal tubular cell mitophagy, whereas inhibition of this signaling pathway protects cells from mitophagy, thus aggravating apoptosis, and ROS production. Accordingly, roxadustat may protect against RIRI-related AKI.


Assuntos
Injúria Renal Aguda , Traumatismo por Reperfusão , Animais , Humanos , Ratos , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/metabolismo , Apoptose , Hipóxia/metabolismo , Hipóxia/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Isquemia , Rim/patologia , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais , Mitofagia , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais
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