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1.
Arq. bras. cardiol ; 119(2): 319-325, ago. 2022. tab
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1383752

ABSTRACT

Resumo Fundamento: Sabe-se que a inflamação desempenha um papel crucial em muitas doenças, incluindo a COVID-19. Objetivo: Utilizando a dilatação fluxo-mediada (DFM), objetivou-se avaliar os efeitos da inflamação na função endotelial de pacientes com COVID-19. Métodos: Este estudo foi realizado com um total de 161 indivíduos, dos quais 80 foram diagnosticados com COVID-19 nos últimos seis meses (48 mulheres e 32 homens com idade média de 32,10±5,87 anos) e 81 eram controles saudáveis (45 mulheres e 36 homens com idade média de 30,51±7,33 anos). Os achados do ecocardiograma transtorácico e da DFM foram analisados em todos os indivíduos. Resultados com p<0,05 foram considerados estatisticamente significantes. Resultados: O ecocardiograma e a DFM do grupo COVID-19 foram realizados 35 dias (intervalo: 25-178) após o diagnóstico. Não houve diferença estatisticamente significativa nos parâmetros ecocardiográficos. Em contraste, a DFM (%) foi significativamente maior no grupo controle (9,52±5,98 versus 12,01±6,18; p=0,01). Na análise multivariada com o modelo stepwise progressivo, a DFM foi significativamente diferente no grupo controle em relação ao grupo COVID-19 (1,086 (1,026-1,149), p=0,04). O teste de correlação de Spearman indicou que a DFM (r=0,27; p=0,006) apresentou correlação positiva fraca com a presença de COVID-19. Conclusão: Os achados deste estudo apontam para disfunção endotelial induzida por COVID-19, avaliada por DFM, na fase inicial de recuperação.


Abstract Background: Inflammation is known to play a crucial role in many diseases, including COVID-19. Objective: Using flow-mediated dilatation (FMD), we aimed to assess the effects of inflammation on endothelial function in COVID-19 patients. Methods: This study was conducted with a total of 161 subjects, of whom 80 were diagnosed with COVID-19 within the last six months (comprising 48 women and 32 men with a mean age of 32.10 ± 5.87 years) and 81 were healthy controls (comprising 45 women and 36 men with a mean age of 30.51 ± 7.33 years). We analyzed the findings of transthoracic echocardiography and FMD in all subjects. All results were considered statistically significant at the level of p < 0.05. Results: The echocardiography and FMD of the COVID-19 group were performed 35 days (range: 25-178) after diagnosis. There was no statistically significant difference in echocardiographic parameters. Differently, FMD (%) was significantly higher in the control group (9.52 ± 5.98 vs. 12.01 ± 6.18, p=0.01). In multivariate analysis with the forward stepwise model, FMD was significantly different in the control group compared to the COVID-19 group (1.086 (1.026 - 1.149), p=0.04). A Spearman's correlation test indicated that FMD (r=0.27, p=0.006) had a weak positive correlation with the presence of COVID-19. Conclusion: Our findings point to COVID-19-induced endothelial dysfunction, as assessed by FMD, in the early recovery phase.

2.
Arq. bras. cardiol ; 118(6): 1134-1140, Maio 2022. tab, graf
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1383694

ABSTRACT

Resumo A aterosclerose é a causa mais comum de doença cardiovascular em todo o mundo, ela está associada a uma alta incidência de eventos clínicos. O acúmulo de evidências elucidou que os RNAs longos não codificantes (LncRNAs) são uma nova classe de transcritos com papéis críticos nos processos fisiopatológicos da aterosclerose. Nesta revisão, resumimos o progresso recente dos LncRNAs no desenvolvimento da aterosclerose. Descrevemos principalmente os diversos mecanismos regulatórios dos LncRNAs nos níveis transcricionais e pós-transcricionais. Este estudo pode fornecer informações úteis sobre os LncRNAs como alvos terapêuticos ou biomarcadores para o tratamento da aterosclerose.


Abstract Atherosclerosis is the most common cause of cardiovascular disease globally, associated with a high incidence of clinical events. Accumulating evidence has elucidated that long non-coding RNAs (lncRNAs) as a novel class of transcripts with critical roles in the pathophysiological processes of atherosclerosis. In this review, we summarize the recent progress of lncRNAs in the development of atherosclerosis. We mainly describe the diverse regulatory mechanisms of lncRNAs at the transcriptional and post-transcriptional levels. This study may provide helpful insights about lncRNAs as therapeutic targets or biomarkers for atherosclerosis treatment.

3.
Rev. Assoc. Med. Bras. (1992) ; 68(2): 147-151, Feb. 2022. tab
Article in English | LILACS | ID: biblio-1365347

ABSTRACT

SUMMARY OBJECTIVE: Beta-thalassemia minor is a blood disease caused by a hereditary decrease in beta-globin synthesis, frequently leading to hypochromic microcytic anemia. Formerly called endothelial cell-specific molecule 1, endocan is a proteoglycan released by vascular endothelial cells in many organs. Our aim was to investigate the relationship between the beta-thalassemia minor patients and the healthy control group in terms of serum endocan level. METHODS: The study was performed in a total of 80 subjects. They were divided into two groups, the beta-thalassemia minor group (n=40) and the healthy control group (n=40). Serum endocan levels, age, sex, body mass index value, and tobacco use data of these groups were compared. RESULTS: No statistically significant difference was detected between the two groups in terms of age, sex, and body mass index values (p>0.05). Endocan levels were measured to be 206.85±88.1 pg/mL in the beta-thalassemia minor group and 236.1±162.8 pg/mL in the control group with no significant difference between the groups in terms of serum endocan levels (p>0.05). CONCLUSIONS: In our study, there was no change in endocan level in beta-thalassemia minor. This might be because serum endocan levels are affected by multi-factorial reasons. Serum endocan levels may be altered secondarily to decreased beta-globin chain, increased sympathetic activity due to anemia, or platelet dysfunction induced by oxidative stress in beta-thalassemia minor. Further multicenter studies involving more patients are necessary to demonstrate this.


Subject(s)
Humans , Proteoglycans , beta-Thalassemia , Neoplasm Proteins , Biomarkers , Body Mass Index , Endothelial Cells
4.
International Eye Science ; (12): 378-382, 2022.
Article in Chinese | WPRIM | ID: wpr-920403

ABSTRACT

@#AIM: To explore the effect of dapagliflozin on the apoptosis and oxidative stress of high glucose-induced human retinal vascular endothelial cells and its regulatory effect on forkhead FOXO4. <p>METHODS: High glucose-induced human retinal vascular endothelial cells(HRVECs)were used to establish a cell injury model(high glucose group). Experimental groups include high glucose+dapagliflozin low-dose group(1ng/L dapagliflozin), high glucose+dapagliflozin medium-dose group(5ng/L dapagliflozin), high glucose+dapagliflozin high-dose group(10ng/L dapagliflozin), high glucose+dapagliflozin high-dose+pcDNA group, high glucose+dapagliflozin high-dose+pcDNA-FOXO4 group, and normal sugar group(5.5mmol/L D-glucose). Flow cytometry was used to detect the apoptosis rate. The levels of superoxide dismutase(SOD)and malondialdehyde(MDA)were tested with corresponding kits. Western blot assay was used to detect the protein level of FOXO4. <p>RESULTS: Compared with the normal sugar group, the apoptosis rate(<i>P</i><0.05), the level of MDA(<i>P</i><0.05)and FOXO4(<i>P</i><0.05)were increased, but the level of SOD was decreased(<i>P</i><0.05)in high-glucose group. Compared with the high glucose group, cell apoptosis rate(<i>P</i><0.05), the level of MDA(<i>P</i><0.05)and the protein level of FOXO4 were decreased(<i>P</i><0.05), but the level of SOD was increased(<i>P</i><0.05)in high glucose+medium-dose dapagliflozin group and high glucose+high-dose dapagliflozin group. Compared with high glucose+dapagliflozin high-dose+pcDNA group, the apoptosis rate(<i>P</i><0.05)and the level of MDA(<i>P</i><0.05)were increased, but the level of SOD was decreased(<i>P</i><0.05)in high glucose+dapagliflozin high-dose+pcDNA-FOXO4 group(<i>P</i><0.05). <p>CONCLUSION: Dapagliflozin could inhibit oxidative stress and cell apoptosis in high glucose-induced HRVECs by down-regulating FOXO4, thereby reducing cell damage.

5.
International Eye Science ; (12): 249-254, 2022.
Article in Chinese | WPRIM | ID: wpr-913032

ABSTRACT

@#Diabetic retinopathy(DR), one of the most common diabetes-specific microvascular complications, is classically described by intraretinal microvascular abnormalities and neovascularization. It is the main reason why visual impairment and blindness in people aged 20-65 years worldwide. Glycolysis can provide energy by converting glucose into pyruvate. Endothelial cells mainly utilize glycolysis to produce ATP to maintain the function, including forming tight junctions and barrier functions. Pyruvate kinase(PK)M2(M2 isoform of pyruvate kinase)is a key enzyme of glycolysis and is widely expressed in most tissues. As major cellular components in the retina, endothelial cells and photoreceptor cells play a crucial role in the occurrence and development of DR. Studies have shown that PKM2 takes part in the development of DR by regulating the function of endothelial cells and photoreceptors in metabolic and non-metabolic ways. Therefore, this article overviews the role of PKM2 in DR from the direction of endothelial cells and photoreceptor cells and provides new insight into the diagnosis and treatment of DR.

6.
Article in Chinese | WPRIM | ID: wpr-928102

ABSTRACT

This study aimed to observe the intervention effect of Jianpi Huogu Formula(JPHGF) on the functional damage of vascular endothelial cells caused by glucocorticoid, and explore its action mechanism from the PI3 K/Akt and mitogen activated protein kinase(MAPK) signaling pathways. The extracted thoracic aorta ring of normal SD rats were intervened first with vascularendothelial growth factor(VEGF, 20 μg·L-1) and/or sodium succinate(MPS, 0. 04 g·L-1) in vitro and then with JPHGF(8, 16, and 32 μg·L-1) for five mcontinuous ethylpdays, rednisolofollowed nebythe statistics of the number, length, and area of microvessels budding fromvascular rings. In addition, the human umbilical vein endothelial cells(HUVECs) induced by VEGF(20 μg·L-1) were added with MPS(0. 04 g·L-1) and then with JPHGF(8, 16, and 32 μg·L-1) for observing the migration, invasion, and luminal formation abilities of HUVECs in the migration, invasion and luminal formation experiments. The protein expression levels of PI3 K, p-Akt, p-JN K, and p-ERK in HUVECs were assayed by Western blot. The results showed that JPHGF dose-dependently improved the num-ber,length, and area of microvessels in MPS-induced rat thoracic aortic ring, reversed the migration, invasion and lumen formation abiliti es of HUVECs reduced by MPS, and up-regulated the protein expression levels of PI3 K, p-Akt, and p-JNK in HUVECs. All thesehave suggested that JPHGF exerts the protective effect against hormone-induced damage to the angiogenesis of vascular endothelial cells by activating the PI3 K/Akt and MAPK signaling pathways, which has provided reference for exploring the mechanism of JPHGF in treating s teroid-induced avascular necrosis of femoral head(SANFH) and also the experimental evidence for enriching the scientific connotationof spleen-invigorating and blood-activating therapy.


Subject(s)
Animals , Glucocorticoids/pharmacology , Human Umbilical Vein Endothelial Cells , Humans , Neovascularization, Pathologic/metabolism , Rats , Rats, Sprague-Dawley , Vascular Endothelial Growth Factor A/metabolism
7.
Article in Chinese | WPRIM | ID: wpr-927994

ABSTRACT

This study explores the regulatory effect of astragaloside Ⅳ on miR-17-5 p and its downstream proprotein convertase subtillisin/kexin type 9(PCSK9)/very low density lipoprotein receptor(VLDLR) signal pathway, aiming at elucidating the mechanism of astragaloside Ⅳ against atherosclerosis(AS). In cell experiment, oxidized low-density lipoprotein(ox-LDL) was used for endothelial cell injury modeling with vascular smooth muscle cells(VSMCs). Then cells were classified into the model group, miR-17-5 p inhibitor group, blank serum group, and astragaloside Ⅳ-containing serum group based on the invention. Afterward, cell viability and the expression of miR-17-5 p, VLDLR, and PCSK9 mRNA and protein in cells in each group were detected. In animal experiment, 15 C57 BL/6 mice were used as the control group, and 45 ApoE~(-/-) mice were classified into the model group, miR-17-5 p inhibitor group, and astragaloside Ⅳ group, with 15 mice in each group. After 8 weeks of intervention, the peripheral serum levels of interleukin-6(IL-6), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α), and the expression of miR-17-5 p, VLDLR, and PCSK9 mRNA in the aorta of mice were detected. The pathological changes of mice in each group were observed. According to the cell experiment, VSMC viability in the miR-17-5 p inhibitor group and the astragaloside Ⅳ-containing serum group was higher than that in the model group(P<0.05). The mRNA and protein expression of miR-17-5 p and VLDLR in VSMCs in the miR-17-5 p inhibitor group and the astragaloside Ⅳ-containing serum group was lower than that in the model group(P<0.05), but the mRNA and protein expression of PCSK9 was higher than that in the model group(P<0.05). As for the animal experiment, the levels of IL-6 and TNF-α in the peripheral serum of the miR-17-5 p inhibitor group and the astragaloside Ⅳ group were lower(P<0.05) and the serum level of IL-10 was higher(P<0.05) than that of the model group. The mRNA expression of miR-17-5 p and VLDLR in the aorta in the miR-17-5 p inhibitor group and the astragaloside Ⅳ group was lower(P<0.05), and PCSK9 mRNA expression was higher(P<0.05) than that in the model group. Pathological observation showed mild AS in the miR-17-5 p inhibitor group and the astragaloside Ⅳ group. In summary, astragaloside Ⅳ can prevent the occurrence and development of AS. The mechanism is that it performs targeted regulation of miR-17-5 p, further affecting the PCSK9/VLDLR signal pathway, inhibiting vascular inflammation, and thus alleviating endothelial cell injury.


Subject(s)
Animals , Atherosclerosis/genetics , Lipoproteins, LDL/metabolism , Mice , MicroRNAs/metabolism , Proprotein Convertase 9/metabolism , Receptors, LDL/metabolism , Saponins , Signal Transduction , Triterpenes
8.
International Eye Science ; (12): 764-768, 2022.
Article in Chinese | WPRIM | ID: wpr-923408

ABSTRACT

@#AIM: To observe the effects of different concentrations of curcumin on the proliferation and expression of VEGF and NF-κB p65 of human retinal capillary endothelial cells(HRCECs)induced by high glucose <i>in vitro</i>.<p>METHODS: The hyperglycemia model of HRCECs in vitro was established by simulating diabetic environment with high glucose medium. The cultured cells were divided into normal control group, high glucose control group, high glucose + 20, 40 and 80μmol/L curcumin groups. The proliferation of HRCECs was detected by CCK-8 assay, and the expression of VEGF and NF-κB p65 was detected by Western-blot and immunocytochemistry.<p>RESULTS: The results of CCK-8 assay showed that high glucose promoted the proliferation of HRCECs significantly compared with the normal control group(<i>P</i><0.01). Curcumin at different concentrations could inhibit the proliferation of cells significantly in a concentration-dependent and time-dependent manner compared with the high glucose control group after being treated with curcumin at different concentrations for 12, 24 and 48h(<i>P</i><0.01). The results of Western-blot showed that compared with the normal control group, the expression of VEGF-A and NF-κB p65 in the high glucose control group was increased significantly(<i>P</i><0.01). Compared with the high glucose control group, the expression of VEGF-A and NF-κB p65 decreased significantly after being treated with curcumin at different concentrations for 12, 24 and 48h, and positively correlated with concentration and time(<i>P</i><0.01). The results of immunocytochemistry showed that the expression of VEGF in the high glucose control group was significantly higher than that in the normal control group(<i>P</i><0.01). After 24h of treatment with curcumin,the expression of VEGF was gradually decreased compared with the high glucose control group(<i>P</i><0.01). There were significant differences in pairwise comparison between each group(<i>P</i><0.01).<p>CONCLUSION: Curcumin can inhibit the proliferation and the expression of VEGF and NF-κB p65 of HRCECs induced by high glucose in a concentration-dependent and time-dependent manner, which may be related to its down-regulation of the expression of VEGF and NF-κB p65.

9.
Journal of Clinical Hepatology ; (12): 832-836, 2022.
Article in Chinese | WPRIM | ID: wpr-923287

ABSTRACT

Objective To establish Cdh5-Cre ERT /Acta2-tdTomato-STOP floxed -eGFP knockin genetic tracing mice, and to investigate its application in studies on vascular endothelial cell transition in liver fibrosis. Methods Cdh5-Cre ERT mice were mated with Acta2-KI mice, and the Cdh5-Cre ERT /Acta2-KI genetic tracing mice were obtained and identified by PCR genotyping. Primary liver sinusoid endothelial cells (LSECs) were isolated and cultured, and a model of CCl 4 -induced liver fibrosis was established. LSECs and liver tissue were collected for immunofluorescent staining to observe the expression of the fluorescent proteins tdTomato and eGFP. Results After being induced by tamoxifen, LSECs and liver tissue of Cdh5-Cre ERT /Acta2-KI genetic tracing mice expressed eGFP under the conditions for epithelial-mesenchymal transdifferentiation established in vivo and in vitro, while the control group without induction expressed tdTomato alone. Conclusion The successfully established Cdh5-Cre ERT /Acta2-KI genetic tracing mice can realize the effective labeling of epithelial-mesenchymal transdifferentiation, which provides a genetic tracing basis for the diverse sources of mesenchymal myofibroblasts in liver fibrosis.

10.
International Eye Science ; (12): 541-548, 2022.
Article in Chinese | WPRIM | ID: wpr-922848

ABSTRACT

@#AIM: To investigate the effect and mechanism of curcumin on inhibiting choroidal neovascularization(CNV)<i>in vitro</i>. METHODS: Human retinal pigment epithelial(ARPE-19)cells chemical hypoxia model was established by cobalt chloride(CoCl2). CCK-8 method was used to detect the effect of curcumin on the activity of ARPE-19 cells induced by CoCl2. RT-qPCR and Western blot were used to detect the expression of AKT, HIF-1α, VEGF mRNA and protein in ARPE-19 cells hypoxia model induced by CoCl2. Cell scratch test, transwell chamber migration test, transwell chamber invasion test and matrigel matrix hose lumen formation test were used to observe the effects of conditioned medium of curcumin in ARPE-19 cells on the proliferation, migration, invasion and lumen formation of human umbilical vein endothelial cells(HUVEC)in non-contact condition. RESULTS:Chemical hypoxia model of ARPE-19 cells can successfully establish by CoCl2 at 100μmol/L. CoCl2 at the final concentration of 100μmol/L can promote the expression of AKT, HIF-1α and VEGF mRNA and p-AKT, HIF-1α and VEGF protein in ARPE-19 cells. Curcumin at the final concentration of 100μmol/L can reduce the expression of AKT, HIF-1α and VEGF mRNA in ARPE-19 hypoxia model. Curcumin at the final concentration of 100μmol/L can reduce the expression of AKT, HIF -1α and VEGF proteins in ARPE-19 hypoxia model. The conditioned medium of low(6.25μmol/L), medium(25μmol/L)and high dose(100μmol/L)curcumin in ARPE-19 cells can significantly inhibit the level migration of HUVEC. The conditioned medium in high dose group can significantly inhibit the vertical migration and cell invasion of HUVEC. The conditioned medium of middle and high dose curcumin in ARPE-19 cells can inhibit the lumen formation of HUVEC. CONCLUSION:Curcumin at 100μmol/L can protect ARPE-19 cells from hypoxia induced by CoCl2. Curcumin can inhibit the formation of blood vessels at the cellular level.

11.
Braz. J. Pharm. Sci. (Online) ; 58: e181092, 2022. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1374550

ABSTRACT

Abstract The present study was designed to examine the effects of atorvastatin on vascular inflammatory responses in human coronary artery endothelial cells(HCAECs), when challenged by lipopolysaccharide (LPS), a Toll-like receptor-4 (TLR4) ligand. HCAECs were pretreated with atorvastatin and induced by LPS. The expression of TLR4, interleukin -6(IL-6), monocyte chemoattractant protein 1(MCP-1), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecular-1(ICAM-1), nuclear factor-κB (NF-κB) and p38 mitogen activated protein kinase(p38 MAPK) were evaluated using Real-time polymerase chain reaction, cytokine ELISA assay and Western blotting. The results showed that pretreatment with atorvastatin down-regulated the expression of TLR4 in LPS-activated HCAECs. Atorvastatin also attenuated the LPS-induced expression of interleukin IL-6 and MCP-1, at both the transcription and translation level in HCAECs. LPS-induced endothelial cell adhesion molecules, ICAM-1 and VCAM-1 expression were also reduced by pretreatment with atorvastatin. Furthermore, atorvastatin efficiently suppressed LPS-induced phosphorylation of NF-κB and p38 MAPK in HCAECs. These findings show that atorvastatin suppresses endothelial cell inflammation, suggesting that atorvastatin may be suitable for development as a therapeutic agent for inflammatory cardiovascular disease.

12.
Clinics ; 77: 100020, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1375186

ABSTRACT

ABSTRACT Objectives: This study aimed to explore the effects of miR-128b in the regulation of Lipopolysaccharide (LPS) induced apoptosis. Methods: Human Pulmonary Microvascular Endothelial Cells (HPMECs) were transfected with an miR-128b inhibitor and stimulated with LPS for 24 h. FCM was performed to detect apoptosis and Reactive Oxygen Species (ROS) production. In addition, miRNA and caspase-3 expression levels were determined using real-time quantitative polymerase chain reaction and western blotting. Results: LPS significantly induced apoptosis and ROS production and upregulated miR-128b and caspase-3 expressions in HPMECs. However, LPS-induced effects were suppressed when an miR-128b inhibitor was used. Preincu-bation with NAC decreased the LPS-induced apoptosis of HPMECs. Conclusions: These effects were mediated by miR-128b via the caspase-3 pathway.

13.
Rev. Assoc. Med. Bras. (1992) ; 67(4): 555-560, Apr. 2021. graf
Article in English | LILACS | ID: biblio-1340629

ABSTRACT

SUMMARY OBJECTIVE: In this study, we aimed at investigating the role of isoleucyl-tRNA synthetase in the growth, migration, and angiogenesis of human umbilical vein endothelial cells and the underlying molecular mechanism. METHODS: To assess the role of isoleucyl-tRNA synthetase, we silenced isoleucyl-tRNA synthetase in human umbilical vein endothelial cells using lentiviral 2 specific short hairpin RNAs (short hairpin RNAs 1 and 2) and examined silencing efficiency using real time quantitative polymerase chain reaction and western blot analyses. Short hairpin RNAs 1-isoleucyl-tRNA synthetase had greater knockdown efficiency, it was used in the entire downstream analysis. Short hairpin RNAs 1- isoleucyl-tRNA synthetase silencing effects on cell proliferation, cell colony generation, cell migration, as well as angiogenesis were assessed using cell counting kit-8, colony development, cell migration, and angiogenesis tube formation assays, respectively. RESULTS: Compared to the control group, anti-isoleucyl-tRNA synthetase short hairpin RNAs significantly silenced isoleucyl-tRNA synthetase expression in human umbilical vein endothelial cells, and suppressed their proliferation, migration, and angiogenic capacity. To characterize the underlying mechanism, western blot analyses showed that isoleucyl-tRNA synthetase knockdown suppressed phosphorylation of extracellular-regulated kinase ½ and protein-serine- threonine kinase, as well as expression of vascular endothelial growth factor, GSK-3β, and β-catenin. CONCLUSIONS: We have shown, for the first time, the critical role of isoleucyl-tRNA synthetase in human umbilical vein endothelial cells. Our data show that isoleucyl-tRNA synthetase knockdown suppresses human umbilical vein endothelial cell proliferation, migration, and angiogenesis. We have also shown that isoleucyl-tRNA synthetase knockdown suppresses phosphorylation of extracellular-regulated kinase ½ and protein-serine- threonine kinase, as well as expression of vascular endothelial growth factor, GSK-3β, and β-catenin. Together, these data highlight isoleucyl-tRNA synthetase as a potential antitumor anti-angiogenic target.


Subject(s)
Humans , Vascular Endothelial Growth Factor A , Cells, Cultured , Cell Proliferation , Human Umbilical Vein Endothelial Cells , Glycogen Synthase Kinase 3 beta
14.
J. vasc. bras ; 20: e20200143, 2021. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1250251

ABSTRACT

Abstract Background There is a spectrum of possibilities for analyzing muscle O2 resaturation parameters for measurement of reactive hyperemia in microvasculature. However, there is no consensus with respect to the responsiveness of these O2 resaturation parameters for assessing reactive hyperemia. Objectives This study investigates the responsiveness of the most utilized muscle O2 resaturation parameters to assess reactive hyperemia in the microvasculature of a clinical group known to exhibit impairments of tissue O2 saturation (StO2). Methods Twenty-three healthy young adults, twenty-nine healthy older adults, and thirty-five older adults at risk of cardiovascular disease (CVD) were recruited. Near-infrared spectroscopy (NIRS) was used to assess StO2 after a 5-min arterial occlusion challenge and the following parameters were analyzed: StO2slope_10s, StO2slope_30s, and StO2slope_until_baseline (upslope of StO2 over 10s and 30s and until StO2 reaches the baseline value); time to StO2baseline and time to StO2max (time taken for StO2 to reach baseline and peak values, respectively); ∆StO2reperfusion (the difference between minimum and maximum StO2 values); total area under the curve (StO2AUCt); and AUC above the baseline value (StO2AUC_above_base). Results Only StO2slope_10s was significantly slower in older adults at risk for CVD compared to healthy young individuals (p < 0.001) and to healthy older adults (p < 0.001). Conversely, time to StO2max was significantly longer in healthy young individuals than in older adult at CVD risk. Conclusions Our findings suggest that StO2slope_10s may be a measure of reactive hyperemia, which provides clinical insight into microvascular function assessment.


Resumo Contexto Existe um espectro de possibilidades na análise dos parâmetros de ressaturação de O2 muscular como uma medida de hiperemia reativa na microvasculatura. No entanto, não há consenso com relação à responsividade desses parâmetros de ressaturação de O2 para avaliação de hiperemia reativa. Objetivos Este estudo investigou a capacidade de resposta dos parâmetros de ressaturação muscular de O2 mais utilizados para avaliar a hiperemia reativa na microvasculatura de um grupo clínico conhecido por apresentar comprometimento da saturação de O2 (StO2). Métodos Foram recrutados 23 jovens saudáveis, 29 idosos saudáveis e 35 idosos com risco para doença cardiovascular. A espectroscopia no infravermelho próximo foi usada para avaliar a StO2 após um teste de oclusão arterial de 5 minutos, no qual os seguintes parâmetros foram analisados: StO2slope_10s, StO2slope_30s e StO2slope_until_baseline (inclinação da StO2 em 10 s, 30 s e até StO2 atingir valores basais); tempo para StO2baseline e tempo para StO2máx (o tempo necessário para StO2 atingir os valores da linha de base e o máximo, respectivamente); ∆StO2reperfusão (a diferença entre o valor de StO2mínimo e StO2máximo); área total sob a curva (StO2AUCt); e área sob a curva acima do valor da linha de base (StO2AUC_above_base). Resultados Apenas StO2slope_10s foi significativamente mais lento em idosos em risco de doença cardiovascular comparados com indivíduos jovens saudáveis (p < 0,001) e idosos saudáveis (p < 0,001). Por outro lado, o tempo para StO2max foi significativamente maior em indivíduos jovens saudáveis do que em idosos em risco de doença cardiovascular. Conclusões Nossos achados sugerem que StO2slope_10s pode ser uma medida de hiperemia reativa, que fornece informações clínicas sobre a avaliação da função microvascular.

15.
China Pharmacy ; (12): 301-308, 2021.
Article in Chinese | WPRIM | ID: wpr-872681

ABSTRACT

OBJECTIVE:To study the effects of the main active components of Naoxintong capsule (NXTC)on the proliferation of human umbilical vein endothelial cell(HUVEC) and its key protein JAK/STAT signal pathway , vasoactive substances ,adhesion molecules and inflammatory factors so as to clarify the m echanism of NXTC for promoting blood circulation and removing blood stasis. METHODS :The effects of different concentration of 12 active components [caffeic acid(1.56-200 μmol/L),ferulic acid (1.56-200 μmol/L),senkyunolide H (3.125-200 μmol/L),n-butylidenephthalide(3.125-200 μmol/L),ligustilide(1.56-200 μmol/L),cryptotanshinone(0.625-80 μmol/L),tanshinol sodium (1.56-200 μmol/L),paeoniflorin (1.56-200 μmol/L),formononetin(1.56-200 μmol/L),salvianolic acid B (1.56-200 μmol/L),catechin(1.56-200 μmol/L)and astragaloside Ⅳ(1.56-200 μmol/L)] on the proliferation of HUVECs were evaluated by CCK- 8 assay. The effects of above active components(3 dose groups ,setting up 0 μmol/L blank control group,hereinafter)on mRNA expression of key proteins JAK 2, STAT3,Akt,ERK in JAK/STAT signal pathway were measured by RT-PCR. The effects of each active component on the expression of PAI- 1,VCAM-1,ICAM-1,VEGF and NF-κB p65 were detected by ELISA. RESULTS :Ferulic acid (6.25,25-200 μg/mL),senkyunolide H (6.25-200 μmol/L),ligustilide(200 μmol/L),cryptotanshinone(10-80 μmol/L),paeoniflorin(1.56, 6.25,12.5 μmol/L),salvianolic acid B (1.56-12.5 μmol/L,200 μmol/L)and catechin (25 μmol/L)could significantly inhibit the proliferation of HUVECs ;caffeic acid (1.56,12.5 μmol/L),ligustilide(50 μmol/L),trashinol sodium (6.25 μmol/L)and paeoniflorin(1.56,100,200 μmol/L)could significantly promote the proliferation of HUVECs (P<0.05 or P<0.01). Compared with blank control group ,mRNA expression of JAK 2,STAT3 and Akt were decreased significantly in some dose groups of ferulic acid,formononetin,salvianolic acid B and astragaloside Ⅳ(P<0.05 or P<0.01);the expression of PAI- 1 were significantly decreased in some dose groups of caffeic acid ,ferulic acid and n-butylphthalide;the expression of ICAM- 1 and VCAM- 1 were decreased significantly in some dose groups of caffeic acid ,ferulic acid ,n-butenylphthalide,cryptotanshinone,formononetin and catechin;the expression of NF-κB p65 were decreased significantly in some dose groups of ferulic acid ,n-butenylphthalide, formononetin,salvianolic acid B and astragaloside Ⅳ;the expression of VEGF were increased significantly in some dose groups of caffeic acid and catechin (P<0.05 or P<0.01). CONCLUSIONS :The active components of Naoxintong capsule may play the role of promoting blood circulation and removing blood stasis by inhibiting the expression of JAK/STAT signal pathway key protein mRNA and PAI- 1,ICAM-1,VCAM-1,NF-κB p65 in HUVEC ,and promoting the expression of VEGF.

16.
Article in Chinese | WPRIM | ID: wpr-906454

ABSTRACT

Objective:To observe the effect of Tongluo Shenggu capsule (TLSGC) on glucocorticoid-induced vascular endothelial cell functional damage, and to preliminally explore the mechanism of action through MEK-ERK signaling pathway. Method:The blood vessel of aorta rings of normal SD rats were induced <italic>in vitro</italic> intervention with methylprednisolone sodium succinate (MPS, 0.04 g·L<sup>-1</sup>) and/or vascular endothelial growth factor (VEGF, 20 μg·L<sup>-1</sup>), and were treated with TLSGC(12.5, 25, 50 μg·L<sup>-1</sup>) continuously for 5 days to observe the number, length and area of microvascular ring buds.In addition, human umbilical vein endothelial cells (HUVEC) induced by VEGF(20 μg·L<sup>-1</sup>) were added into MPS(0.04 g·L<sup>-1</sup>) and TLSGC (12.5, 25, 50 μg·L<sup>-1</sup>) were added. Then, Transwell migration, Transwell invasion and lumen formation experiments were used to detect the migration, invasion and lumen formation ability of HUVEC, respectively. The content of nitric oxide(NO) in the cell supernatant was detected by nitrate reductase method, the content of endothelin 1(ET-1) in the cell supernatant was detected by dry powder method. Moreover, the protein contents of vascular endothelial growth factor receptor 2 (VEGFR2), extracellular signal-regulated kinase (ERK), phospho-extracellular signal-regulated kinase (p-ERK), mitogen extracellular kinase1(MEK) and phosphorylated mitogen extracellular kinase1(p-MEK) in the cells were determined by Western blot. Result:Compared with the normal group, MPS could significantly inhibit the number, length and area of VEGF-induced rat thoracic aortic ring microvessels, HUVEC cell migration, invasion and lumen formation ability. It could reduce NO content and increase ET-1 content. MPS could also significantly reduce the protein content of VEGF-induced VEGFR2, p-MEK and p-ERK in HUVEC(<italic>P</italic><0.05,<italic>P</italic><0.01). Compared with the model group, TLSGC could dose-dependently increase the number, length and area of MPS-induced abnormally reduced rat thoracic aortic ring microvessels, promote MPS-induced abnormally decreased HUVEC cell migration, invasion and lumen formation ability. It could increase the protein contents of NO, VEGFR2, p-MEK and p-ERK in HUVEC, and reduce abnormally increased ET-1 content(<italic>P</italic><0.05<italic>,P</italic><0.01). Conclusion:TLSGC has a protective effect on the damage of angiogenesis and secretion of vascular endothelial cells induced by glucocorticoid, and the mechanism may be related to the activation of MEK/ERK signaling pathway.

17.
Article in Chinese | WPRIM | ID: wpr-906295

ABSTRACT

Objective:To study the protective effect of essential oil from Alpiniae Zerumbet Fructus (EOAZF) against high glucose (HG)-induced injury of human umbilical vein endothelial cells (HUVECs) <italic>in vitro</italic>, so as to provide experimental evidence for the treatment of diabetes-induced cardiovascular diseases with EOAZF. Method:The cells were divided into the normal group, model group (25 mmol·L<sup>-1</sup> glucose), positive control group (100 mg·L<sup>-1</sup> vitamin C), and the low- (0.25 μg·L<sup>-1</sup>), medium- (1 μg·L<sup>-1</sup>), and high-dose (4 μg·L<sup>-1</sup>) EOAZF groups. The HUVECs were damaged by HG. The secretion amounts of malondialdehyde (MDA), nitric oxide (NO), and endothelin-1 (ET-1) in HUVECs of different groups were measured to assess the protective effect of EOAZF against HG-induced injury. The effects of EOAZF on the apoptosis and reactive oxygen species (ROS) generation of HUVECs damaged by HG were detected by Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) staining and dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay. The protein and mRNA expression levels of thioredoxin interacting protein (TXNIP) and thioredoxin 1 (Trx-1) were determined by Western blot and Real-time polymerase chain reaction (Real-time PCR), followed by the measurement of total intracellular Trx-1 activity with insulin disulfide reduction method. Result:The comparison with the control group revealed that the proliferation of HUVECs in the model group was significantly inhibited and their shape was damaged. Compared with the model group, EOAZF protected HUVECs against HG-induced injury in a concentration-dependent manner. The secretion amounts of MDA and ET-1 (<italic>P</italic><0.05) in the model group were increased in contrast to those in the control group, while the NO level was decreased (<italic>P</italic><0.01). Compared with the model group, EOAZF at all the three concentrations, especially at 4 μg·L<sup>-1</sup>, obviously reduced the secretion of MDA and ET-1 (<italic>P</italic><0.05), but elevated NO after HG induction (<italic>P</italic><0.05). The cell apoptosis assay and ROS detection results demonstrated that the apoptosis and ROS level in the model group were higher than those in the control group (<italic>P</italic><0.01). Compared with the model group, EOAZF at 4 μg·L<sup>-1 </sup>significantly lowered the ROS level and apoptosis (<italic>P</italic><0.05) of HUVECs damaged by HG. The Western blot assay and Trx-1 activity detection uncovered that the protein and mRNA expression levels of TXNIP in the model group were significantly up-regulated as compared with those in the control group (<italic>P</italic><0.05), whereas the Trx-1 activity was decreased (<italic>P</italic><0.01). Compared with the model group, EOAZF at 4 μg·L<sup>-1 </sup>significantly down-regulated the mRNA and protein (<italic>P</italic><0.05) expression levels of TXNIP and enhanced the total Trx-1 activity (<italic>P</italic><0.05) in HUVECs, thus suppressing the oxidative stress. Conclusion:EOAZF exerts the protective effects against HG-induced injury in HUVECs by improving the endothelial function and reducing intracellular ROS and apoptosis. Its efficacy in anti-oxidative stress may be related to the down-regulation of mRNA and protein expression levels of TXNIP and the enhancement of Trx-1 activity.

18.
Article in Chinese | WPRIM | ID: wpr-906199

ABSTRACT

Objective:To study the effects of Fangji Huangqitang(FJHQT) on migration, adhesion,invasion and tube formation of human umbilical vein endothelial cells (HUVECs) induced by vascular endothelial growth factor (VEGF). Method:HUVECs were induced by VEGF (20 μg·L<sup>-1</sup>) <italic>in vitro</italic>. The effects of FJHQT (0.25,0.5,1 g·L<sup>-1</sup>) on HUVECs were detected by methyl thiazolyl tetrazolium(MTT), scratch repair, transwell migration, adhesion, invasion and tube formation. Protein in HUVECs was extracted and protein expression levels of phosphorylated Janus kinase 1 (p-JAK1) were detected by Western blot. Result:Compared with control group, VEGF (20 μg·L<sup>-1</sup>) can increase the proliferation, scratch repair, transwell migration, adhesion, invasion and tube formation of HUVECs cells (<italic>P</italic><0.01), compared with VEGF group, FJHQT (0.25,0.5,1 g·L<sup>-1</sup>) ,there is no significant effect on the proliferation of HUVECs induced by VEGF for 24 hours, but it can significantly reduce the scratch repair, migration, adhesion, invasion and tube formation of HUVECs induced by VEGF within 24 hours (<italic>P</italic><0.05). Compared with blank group, VEGF could induce abnormal elevation of p-JAK1 in HUVECs (<italic>P</italic><0.01), while FJHQT (0.25,0.5,1 g·L<sup>-1</sup>) could significantly reduce the expression levels of p-JAK1 (<italic>P</italic><0.05,<italic>P</italic><0.01). Conclusion:FJHQT can inhibit the migration, adhesion and invasion of HUVECs, the mechanism may be related to JAK1.

19.
Article in Chinese | WPRIM | ID: wpr-906174

ABSTRACT

Objective:To investigate the effect of Ginseng Radix et Rhizoma-Notoginseng Radix et Rhizoma-Chuanxiong Rhizoma extract on endothelial microparticles (EMPs)-induced vascular endothelial cell senescence, and explore the possible mechanism. Method:Human umbilical vein endothelial cells (HUVECs) were used as the research objects, and the aged model was established with 10-12 passages of replicative senescence cells. The experimental cells were divided into young group (2-4 passage cells), aged group (10-12 passage cells), only EMPs intervention group (extract EMPs produced by aged cells to intervene young cells) and low dose, middle dose and high dose drug intervention groups (200, 300, 400 mg·L<sup>-1</sup>). Senescence related <italic>β</italic>-galactosidase (SA-<italic>β</italic>-gal) staining and cell cycle propidium iodide (PI) staining were used to determine cell senescence. Cell counting kit-8 (CCK-8) assay was used to screen the drug concentration. EMPs were extracted by two-step centrifugation, EMPs labeled with phycoerythrin (PE) anti-human CD31 antibody or fluorescein isothiocyanate (FITC) annexin V were detected by flow cytometry, intracellular reactive oxygen species (ROS) were detected by 2',7'- dichlorofluorescein diacetate (DCFDA) staining. Result:After treatment with the drug, SA-<italic>β</italic>-gal activity of the aged cells significantly decreased (<italic>P</italic><0.01), the S phase arrest was restored (<italic>P</italic><0.01), and the number of CD31<sup>+</sup> EMPs and annexin V<sup>+</sup> EMPs secreted by aged cells decreased (<italic>P</italic><0.05). Compared with the young group, only EMPs intervention group could induce increased SA-<italic>β</italic>-gal activity and S phase arrest in young cells (<italic>P</italic><0.05,<italic>P</italic><0.01). However, after intervention of EMPs and the drug, EMPs-mediated increase of SA-<italic>β</italic>-gal activity was significantly inhibited and S phase arrest was restored (<italic>P</italic><0.05). The increase of intracellular ROS induced by EMPs was also significantly inhibited by the drug (<italic>P</italic><0.05,<italic>P</italic><0.01). Conclusion:Ginseng Radix et Rhizoma-Notoginseng Radix et Rhizoma-Chuanxiong Rhizoma extract can delay the senescence of vascular endothelial cells by influencing EMPs, and the mechanism may be related to the inhibition of increased intracellular ROS induced by EMPs.

20.
Article in Chinese | WPRIM | ID: wpr-906048

ABSTRACT

Objective:To explore the effect of Duanteng Yimu decoction (DTYM) on the activation of the human umbilical vein endothelial cell (HUVEC) model and the effect on related activated proteins and vascular endothelial growth factor (VEGF) signaling pathway. Method:After DTYM (200, 400 g·mL<sup>-1</sup>) treatment of HUVEC induced by VEGF and tumor necrosis factor-<italic>α</italic> (TNF-<italic>α</italic>), cell proliferation, migration, and tubulogenesis were detected by cell counting kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, transwell migration assay, phalloidin staining, and matrix gel card method. The mRNA expression of adhesion factors, including E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) was detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The expression of von Willebrand factor (VWF), platelet-endothelial cell adhesion molecule-31 (CD31), angiogenic factor cysteine-rich-61 (CYR61), angiopoietin-1 (ANG-1), VEGF, and VEGF receptor-2 (VEGFR2) was detected by Western blot. Immunofluorescence was used to determine CD31 expression. Result:Compared with the normal group, the model group showed potentiated proliferation, migration, and tubulogenesis of HUVEC (<italic>P</italic><0.05, <italic>P</italic><0.01), elevated mRNA expression of E-selectin, ICAM-1, and VCAM-1 (<italic>P</italic><0.01), up-regulated protein expression of VWF, CD31, ANG-1, CYR61, VEGF-<italic>α</italic>, and phospho (p)-VEGFR2 (<italic>P</italic><0.05,<italic> P</italic><0.01), and increased CD31 immunofluorescence intensity (<italic>P</italic><0.01). Compared with the model group, the DTYM groups displayed blunted proliferation, migration, and tubulogenesis of HUVEC (<italic>P</italic><0.05,<italic> P</italic><0.01), decreased mRNA expression of E-selectin, ICAM-1, and VCAM-1 (<italic>P</italic><0.05, <italic>P</italic><0.01), down-regulated protein expression of VWF, CD31, ANG-1, CYR61, VEGF-<italic>α</italic>, and p-VEGFR2 (<italic>P</italic><0.05, <italic>P</italic><0.01), and weakened CD31 immunofluorescence intensity (<italic>P</italic><0.01). Conclusion:DTYM inhibits HUVEC proliferation, migration, adhesion, and tubulogenesis, which is associated with the regulation of CD31, VWF, CYR61, and ANG-1 expression in HUVEC and the VEGF signaling pathway.

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