RESUMO
INTRODUCTION: Fibrosing mediastinitis (FM) is a rare disease characterized by excessive proliferation of fibrous tissue in the mediastinum and can cause bronchial stenosis, superior vena cava obstruction, pulmonary artery and vein stenosis, etc. CASE PRESENTATION: An aging patient with intermittent chest tightness and shortness of breath was diagnosed with FM associated pulmonary hypertension (FM-PH) by echocardiography and enhanced CT of the chest, and CT pulmonary artery (PA)/ pulmonary vein (PV) imaging revealed PA and PV stenosis. Selective angiography revealed complete occlusion of the right upper PV, and we performed endovascular intervention of the total occluded PV. After failure of the antegrade approach, the angiogram revealed well-developed collaterals of the occluded RSPV-V2b, so we chose to proceed via the retrograde approach. We successfully opened the occluded right upper PV and implanted a stent. CONCLUSIONS: This report may provide new management ideas for the interventional treatment of PV occlusion.
Assuntos
Veias Pulmonares , Stents , Humanos , Resultado do Tratamento , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/fisiopatologia , Veias Pulmonares/cirurgia , Doença Crônica , Pneumopatia Veno-Oclusiva/terapia , Pneumopatia Veno-Oclusiva/diagnóstico por imagem , Pneumopatia Veno-Oclusiva/fisiopatologia , Pneumopatia Veno-Oclusiva/etiologia , Estenose de Veia Pulmonar/diagnóstico por imagem , Estenose de Veia Pulmonar/terapia , Estenose de Veia Pulmonar/fisiopatologia , Estenose de Veia Pulmonar/etiologia , Mediastinite/diagnóstico , Mediastinite/terapia , Masculino , Flebografia , Angioplastia com Balão/instrumentação , Idoso , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/terapia , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/diagnóstico por imagem , Fibrose , Circulação Colateral , Circulação Pulmonar , FemininoRESUMO
Rho kinase (ROCK) is implicated in the development of pulmonary arterial hypertension (PAH) in which abnormal pulmonary vascular smooth muscle (VSM) contractility and remodeling lead to right heart failure. Pharmacologic ROCK inhibitors block experimental pulmonary hypertension (PH) development in rodents but can have off-target effects and do not distinguish between the two ROCK forms, ROCK1 and ROCK2, encoded by separate genes. An earlier study using gene knock out (KO) in mice indicated that VSM ROCK2 is required for experimental PH development, but the role of ROCK1 is not well understood. Here we investigated the in vivo role of ROCK1 in PH development by generating a VSM-targeted homozygous ROCK1 gene KO mouse strain. Adult control mice exposed to Sugen5416 (Su)/hypoxia treatment to induce PH had significantly increased right ventricular systolic pressures (RVSP) and RV hypertrophy versus normoxic controls. In contrast, Su/hypoxia-exposed VSM ROCK1 KO mice did not exhibit significant RVSP elevation, and RV hypertrophy was blunted. Su/hypoxia-induced pulmonary small vessel muscularization was similarly elevated in both control and VSM ROCK1 KO animals. siRNA-mediated ROCK1 knock-down (KD) in human PAH pulmonary arterial SM cells (PASMC) did not affect cell growth. However, ROCK1 KD led to reduced AKT and MYPT1 signaling in serotonin-treated PAH PASMC. The findings suggest that like VSM ROCK2, VSM ROCK1 actively contributes to PH development, but in distinction acts via nonproliferative pathways to promote hypoxemia, and thus may be a distinct therapeutic target in PH.
Assuntos
Hipertensão Arterial Pulmonar , Quinases Associadas a rho , Animais , Hipertrofia Ventricular Direita/genética , Hipóxia/complicações , Camundongos , Camundongos Knockout , Músculo Liso Vascular/enzimologia , Miócitos de Músculo Liso/metabolismo , Hipertensão Arterial Pulmonar/genética , Artéria Pulmonar/metabolismo , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismo , Quinases Associadas a rho/fisiologiaRESUMO
Macrophage infiltration and activation in myocardium are hallmarks of acute cardiac inflammatory response to high blood pressure. However, the underlying mechanisms remain elusive. In this article, we report that CD8(+) T cells are required for cardiac recruitment and activation of macrophages. First, mice with CD8 gene-targeted (CD8 knockout) or CD8(+) T cells depleted by Ab showed significantly reduced cardiac inflammatory response to the elevation of blood pressure after angiotensin II (Ang II) infusion, whereas CD8 knockout mice reconstituted with CD8(+) T cells restored the sensitivity to Ang II. More importantly, CD8(+) T cells were required for macrophage infiltration in myocardium and subsequent activation to express proinflammatory cytokines and chemokines. Furthermore, macrophage activation required direct contact with activated CD8(+) T cells, but with TCR dispensable. TCR-independent activation of macrophages was further confirmed in MHC class I-restricted OVA-specific TCR transgenic mice, which showed a CD8(+) T cell activation and cardiac proinflammatory response to Ang II similar to that of wild-type mice. Finally, only myocardium-infiltrated, but not peripheral, CD8(+) T cells were specifically activated by Ang II, possibly by the cardiac IFN-γ that drove IFN-γR(+) CD8(+) T cell infiltration and activation. Thus, this work identified a TCR-independent innate nature of CD8(+) T cells that was critical in initiating the sterile immune response to acute elevation of blood pressure.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Hipertensão/imunologia , Miocárdio/imunologia , Transferência Adotiva , Angiotensina II , Animais , Antígenos CD8/genética , Antígenos CD8/imunologia , Antígenos CD8/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/transplante , Citocinas/genética , Citocinas/imunologia , Citocinas/metabolismo , Fibrose/imunologia , Citometria de Fluxo , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Ativação Linfocitária/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos da Linhagem 129 , Camundongos Knockout , Camundongos Transgênicos , Miocárdio/metabolismo , Miocárdio/patologia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
OBJECTIVE: The goal of the present study was to investigate the correlation between serum 25-hydroxyvitamin D [25(OH)D] levels and disease remission in Takayasu arteritis (TAK) patients. METHODS: This retrospective study included 59 patients in the study group and 80 patients in the validation cohort with TAK. After 6 months of therapy, patients were re-evaluated, and serum 25(OH)D levels were compared before and after treatment. Correlations between changes in 25(OH)D levels and changes in disease activity scores (NIH, ITAS2010, ITAS.A) were analyzed. Additionally, a predictive cut-off value for disease remission was determined. RESULTS: After 6 months of therapy, serum 25(OH)D levels in TAK patients significantly increased compared to baseline [(18.33 ± 7.25)µg/L vs (11.77 ± 4.14) µg/L] (P < 0.001). Positive correlations were observed between the increasing changes in the 25(OH)D level and the decreasing changes in the reduced NIH, ITAS2010, and ITAS.A scores (r = 0.455, P < 0.001; r = 0.495, P < 0.001; and r = 0.352 P = 0.006, respectively). A change of 8.45 µg/L in 25(OH)D level was identified as the predictive cut-off value for TAK remission (sensitivity 54.1%, specificity 90.9%, area under the curve = 0.741). Similarly for patients with normal baseline ESR, sensitivity is 68.0%, specificity is 92.3%, and area under the curve is 0.831, and for patients with normal baseline CRP, sensitivity is 58.3%, specificity is 90.0%, and area under the curve is 0.748. Validation in an additional 80 patients demonstrated a higher remission rate in those with a 25(OH)D level change > 8.45 µg/L. CONCLUSION: Serum 25(OH)D levels significantly increased after treatment in TAK patients, and an increase of ≥ 8.45 µg/L was predictive of disease remission, especially in individuals with normal baseline ESR and/or CRP levels. Key Points ⢠Following treatment, there was a significant increase in serum 25(OH)D levels among TAK patients. ⢠The elevated changes in 25(OH)D levels before and after treatment demonstrated a positive correlation with the reduction in disease activity scores. ⢠In patients with TAK before and after treatment, an elevation in serum 25(OH)D levels exceeding 8.45 µg/L serves as an indicator for disease remission, particularly prominent in individuals with normal baseline ESR and/or CRP levels.
Assuntos
Sedimentação Sanguínea , Proteína C-Reativa , Indução de Remissão , Arterite de Takayasu , Vitamina D , Humanos , Feminino , Estudos Retrospectivos , Masculino , Vitamina D/análogos & derivados , Vitamina D/sangue , Adulto , Arterite de Takayasu/sangue , Arterite de Takayasu/tratamento farmacológico , Proteína C-Reativa/metabolismo , Proteína C-Reativa/análise , Adulto Jovem , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adolescente , Biomarcadores/sangueRESUMO
Pulmonary hypertension (PH) pathogenesis is driven by inflammatory and metabolic derangements as well as glycolytic reprogramming. Induction of both interleukin 6 (IL6) and transglutaminase 2 (TG2) expression participates in human and experimental cardiovascular diseases. However, little is known about the role of TG2 in these pathologic processes. The current study aimed to investigate the molecular interactions between TG2 and IL6 in mediation of tissue remodeling in PH. A lung-specific IL6 over-expressing transgenic mouse strain showed elevated right ventricular (RV) systolic pressure as well as increased wet and dry tissue weights and tissue fibrosis in both lungs and RVs compared to age-matched wild-type littermates. In addition, IL6 over-expression induced the glycolytic and fibrogenic markers, hypoxia-inducible factor 1α, pyruvate kinase M2 (PKM2), and TG2. Consistent with these findings, IL6 induced the expression of both glycolytic and pro-fibrogenic markers in cultured lung fibroblasts. IL6 also induced TG2 activation and the accumulation of TG2 in the extracellular matrix. Pharmacologic inhibition of the glycolytic enzyme, PKM2 significantly attenuated IL6-induced TG2 activity and fibrogenesis. Thus, we conclude that IL6-induced TG2 activity and cardiopulmonary remodeling associated with tissue fibrosis are under regulatory control of the glycolytic enzyme, PKM2.
Assuntos
Fibroblastos , Proteínas de Ligação ao GTP , Hipertensão Pulmonar , Interleucina-6 , Pulmão , Camundongos Transgênicos , Proteína 2 Glutamina gama-Glutamiltransferase , Piruvato Quinase , Transglutaminases , Animais , Humanos , Camundongos , Modelos Animais de Doenças , Fibroblastos/metabolismo , Fibrose , Proteínas de Ligação ao GTP/metabolismo , Proteínas de Ligação ao GTP/genética , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/etiologia , Interleucina-6/metabolismo , Pulmão/patologia , Pulmão/imunologia , Pulmão/metabolismo , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Piruvato Quinase/metabolismo , Piruvato Quinase/genética , Transglutaminases/metabolismo , Transglutaminases/genéticaRESUMO
PURPOSE: Platelets are essential for primary hemostasis; however, platelet activation also plays an important proinflammatory role. Inflammation promotes the development of cardiac fibrosis and heart failure induced by hypertension. In this study, we aimed to determine whether inhibiting platelet activation using clopidogrel could inhibit hypertension-induced cardiac inflammation and fibrosis. METHODS: Using a mouse model of angiotensin II (Ang II) infusion (1,500 ng/[kg·min] for 7 days), we determined the role of platelet activation in Ang II infusion-induced cardiac inflammation and fibrosis using a P2Y12 receptor inhibitor, clopidogrel (50 mg/[kg·day]). RESULTS: CD41 staining showed that platelets accumulated in Ang II-infused hearts. Clopidogrel treatment inhibited Ang II infusion-induced accumulation of α-SMA(+) myofibroblasts and cardiac fibrosis (4.17 ± 1.26 vs. 1.46 ± 0.81, p < 0.05). Infiltration of inflammatory cells, including Mac-2(+) macrophages and CD45(+)Ly6G(+) neutrophils (30.38 ± 4.12 vs. 18.7 ± 2.38, p < 0.05), into Ang II-infused hearts was also suppressed by platelet inhibition. Real-time PCR and immunohistochemical staining showed that platelet inhibition significantly decreased the expression of interleukin-1ß and transforming growth factor-ß. Acute injection of Ang II or PE stimulated platelet activation and platelet-leukocyte conjugation, which were abolished by clopidogrel treatment. CONCLUSION: Thus, inhibition of platelet activation by clopidogrel prevents cardiac inflammation and fibrosis in response to Ang II. Taken together, our results indicate Ang II infusion-induced hypertension stimulated platelet activation and platelet-leukocyte conjugation, which initiated inflammatory responses that contributed to cardiac fibrosis.
Assuntos
Fibrose/prevenção & controle , Hipertensão/complicações , Miocardite/prevenção & controle , Inibidores da Agregação Plaquetária/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticlopidina/análogos & derivados , Angiotensina II , Animais , Clopidogrel , Fibrose/patologia , Hipertensão/induzido quimicamente , Hipertensão/patologia , Hipertensão/fisiopatologia , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocardite/patologia , Miocárdio/patologia , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Ticlopidina/farmacologia , Ticlopidina/uso terapêutico , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismoRESUMO
BACKGROUND: With the gradual adoption of new metabolic-associated fatty liver disease (MAFLD) definitions in clinical practice, the relationship between MAFLD and cardiovascular disease (CVD) risk remains unclear. Similarly, clinical differences between MAFLD and nonalcoholic fatty liver disease (NAFLD), and the relationship between MAFLD and CVD risk are unclear. METHODS: We conducted a retrospective study using the 1988-1994 National Health and Nutrition Examination Surveys (NHANES III) database, including 11,673 individuals. Multivariate logistic regression analysis was performed to test relationships between MAFLD and the 10-year CVD risk. RESULTS: MAFLD was more significant than NAFLD in medium/high 10-year CVD risk (according to Framingham risk score) (1064 (29.92%) vs. 1022 (26.37%), P < 0.005). MAFLD patients were stratified according to NAFLD fibrosis scores (NFS's). In univariate regression analysis, when compared with non-MAFLD patients, unadjusted-OR values for MAFLD with different liver fibrosis stages, which were tiered by NFS (NFS < -1.455,-1.455 ≤ NFS < 0.676, and NFS ≥ 0.676) in the medium 10-year CVD risk (according to Framingham scores) were 1.175 (95% CI 1.030-1.341), 3.961 (3.449-4.549), and 5.477 (4.100-7.315), and the unadjusted or values of different MAFLD groups in the high 10-year CVD risk were 1.407 (95% CI 1.080-1.833), 5.725 (4.500-7.284), and 5.330 (3.132-9.068). Then, after adjusting for age, sex, race, alcohol consumption, and smoking, or adjusting for age, race, alcohol consumption, smoking, type 2 diabetes mellitus (T2DM), and other confounding factors, the incidence of medium and high 10-year CVD risk was statistically significant (P < 0.05). CONCLUSIONS: We showed that patients with MAFLD had a higher 10-year CVD risk when compared with patients with NAFLD. Increased MAFLD hepatic fibrosis scores were associated with a 10-year CVD risk.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Inquéritos Nutricionais , Estudos RetrospectivosRESUMO
OBJECTIVE: This study aimed to investigate the imaging and serological features in Takayasu arteritis (TA) patients with valvular involvement and determine the relationship between them. METHOD: This is a retrospective single-center study enrolled 103 TA patients fulfilling the American College of Rheumatology criteria. An independent medical chart review was performed by two senior rheumatologists from Beijing Anzhen Hospital, Capital Medical University. The logistic analysis was used to investigate the relationship between valvular involvement in TA patients and the imaging and serological features of them. RESULTS: Sixty-six TA patients (64.08%) had cardiac valvular involvement in our study. Aortic insufficiency (62.12%) was the most common valvular involvement. Twelve (22.22%) patients developed heart failure. In patients with valvular involvement, the most common angiographic type was Numano type V, which was significantly higher than that in patients without valvular involvement (53.30% vs 32.43%, p = 0.044), followed by coronary involvement (28.79% vs 10.81%, p = 0.036) and Numano type IIb (21.21% vs 5.41%, p = 0.034). Serum levels of immunoglobulin A (2.84 ± 1.42 g/L vs 2.26 ± 0.97 g/L, p = 0.032) and immunoglobulin G (13.5 ± 4.71 g/L vs 11.42 ± 3.01 g/L, p = 0.015) were significantly higher in patients with valvular involvement. Numano type IIb is significantly related to moderate-severe aortic valvular regurgitation in TA patients (4.10 [1.03-16.33], p = 0.04). Elevated C-reactive protein (CRP) level is associated with moderate-severe mitral valve involvement in TA patients (p = 0.05, OR = 17.75, 95% CI 1.07-295.41). CONCLUSIONS: CRP elevation and Numano type IIb are significantly related to different types of valvular involvement in TA patients. Key Points ⢠The Numano types IIb and V were common in TA patients with valvular involvement. ⢠CRP elevation and Numano type IIb are close related to valvular involvement in TA patient. ⢠Echocardiogram screening and CRP level examination are reasonable to TA patients which might have valvular involvement.
Assuntos
Insuficiência da Valva Aórtica , Arterite de Takayasu , Insuficiência da Valva Aórtica/diagnóstico por imagem , Ecocardiografia , Coração , Humanos , Estudos Retrospectivos , Arterite de Takayasu/complicações , Arterite de Takayasu/diagnóstico por imagemRESUMO
BACKGROUND: Takayasu's arteritis (TA) may involve the pulmonary artery, which signifies a poor prognosis. This study investigated the features of TA patients with pulmonary artery involvement. METHODS: One hundred and twenty-six inpatients diagnosed with TA were retrospectively studied. The clinical data of TA patients with and without pulmonary artery involvement were compared. The imaging features of pulmonary artery lesions in TA patients were evaluated. The treatment responses of pulmonary artery lesions were described, and the drug regimens in different treatment response groups were compared. RESULTS: Among the patients with TA, 15.9% showed associated pulmonary artery involvement. The disease durations were significantly longer in patients with pulmonary artery involvement than in those without (108.0 months (53.5, 222.0) vs. 36.0 months (12.0, 120.0); p = 0.038). Hemoptysis was more common in TA patients with pulmonary artery involvement than in those without (15.0%, 3 cases vs. 0.0%; p < 0.001). TA patients with disease duration longer than 5 years showed a 3.42-fold higher odds of pulmonary artery involvement than those with a disease duration of less than 5 years (adjusted odds ratio, 3.42 (95% confidence interval, 1.20-9.76); p = 0.02). The most common imaging manifestations of pulmonary artery involvement were stenosis and occlusion. Among the six patients who had good response to treatment of pulmonary artery lesions, five were treated with the interleukin-6 receptor antagonist tocilizumab. CONCLUSIONS: TA patients with pulmonary artery involvement have a longer course of disease and more symptoms of hemoptysis. TA-related pulmonary artery lesions more commonly manifested as stenosis and occlusion. Tocilizumab may be effective for TA-related pulmonary vascular disease. Key Points ⢠Disease duration longer than 5 years is associated with pulmonary artery involvement in TA. ⢠Hemoptysis is a characteristic clinical symptom of TA with pulmonary artery involvement. ⢠Tocilizumab may be more effective for pulmonary artery lesions of TA.
Assuntos
Arterite de Takayasu , China , Humanos , Artéria Pulmonar/diagnóstico por imagem , Estudos Retrospectivos , Arterite de Takayasu/complicações , Arterite de Takayasu/diagnóstico por imagem , Arterite de Takayasu/tratamento farmacológicoRESUMO
BACKGROUND: The postthrombotic syndrome is a common, often morbid sequela of venous thrombosis (VT) that arises from thrombus persistence and inflammatory scarring of juxtaposed vein walls and valves. Noninvasive 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging can measure neutrophil inflammation in VT. Here, we hypothesized (1) early fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) VT inflammation can predict subsequent vein wall scarring (VWS) and (2) statin therapy can reduce FDG-PET VT inflammation and subsequent VWS. METHODS: C57BL/6J mice (n=75) underwent induction of stasis-induced VT of the inferior vena cava or jugular vein. Inferior vena cava VT mice (n=44) were randomized to daily oral rosuvastatin 5 mg/kg or saline starting at day -1. Subgroups of mice then underwent FDG-PET/CT 2 days after VT induction. On day 14, a subset of mice was euthanized, and VWS was assessed via histology. In vitro studies were further performed on bone marrow-derived neutrophils. RESULTS: Statin therapy reduced early day 2 FDG-PET VT inflammation, thrombus neutrophil influx, and plasma IL (interleukin)-6 levels. At day 14, statin therapy reduced VWS but did not affect day 2 thrombus mass, cholesterol, or white blood counts, nor reduce day 2 glucose transporter 1 or myeloperoxidase expression in thrombus or in isolated neutrophils. In survival studies, the day 2 FDG-PET VT inflammation signal as measured by mean and maximum standardized uptake values predicted the extent of day 14 VWS (area under the receiver operating characteristic curve =0.82) with a strong correlation coefficient (r) of r=0.73 and r=0.74, respectively. Mediation analyses revealed that 40% of the statin-induced VWS reduction was mediated by reductions in VT inflammation as quantified by FDG-PET. CONCLUSIONS: Early noninvasive FDG-PET/CT imaging of VT inflammation predicts the magnitude of subsequent VWS and may provide a new translatable approach to identify individuals at risk for postthrombotic syndrome and to assess anti-inflammatory postthrombotic syndrome therapies, such as statins.
Assuntos
Cicatriz/diagnóstico , Fluordesoxiglucose F18/farmacologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Veias/diagnóstico por imagem , Trombose Venosa/diagnóstico , Animais , Cicatriz/etiologia , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Compostos Radiofarmacêuticos/farmacologia , Trombose Venosa/etiologiaRESUMO
Abnormalities that characterize pulmonary arterial hypertension include impairment in the structure and function of pulmonary vascular endothelial and smooth muscle cells. Aldosterone levels are elevated in human pulmonary arterial hypertension and in experimental pulmonary hypertension, while inhibition of the aldosterone-binding mineralocorticoid receptor attenuates pulmonary hypertension in multiple animal models. We explored the role of mineralocorticoid receptor in endothelial and smooth muscle cells in using cell-specific mineralocorticoid receptor knockout mice exposed to sugen/hypoxia-induced pulmonary hypertension. Treatment with the mineralocorticoid receptor inhibitor spironolactone significantly reduced right ventricular systolic pressure. However, this is not reproduced by selective mineralocorticoid receptor deletion in smooth muscle cells or endothelial cells. Similarly, spironolactone attenuated the increase in right ventricular cardiomyocyte area independent of vascular mineralocorticoid receptor with no effect on right ventricular weight or interstitial fibrosis. Right ventricular perivascular fibrosis was significantly decreased by spironolactone and this was reproduced by specific deletion of mineralocorticoid receptor from endothelial cells. Endothelial cell-mineralocorticoid receptor deletion attenuated the sugen/hypoxia-induced increase in the leukocyte-adhesion molecule, E-selectin, and collagen IIIA1 in the right ventricle. Spironolactone also significantly reduced pulmonary arteriolar muscularization, independent of endothelial cell-mineralocorticoid receptor or smooth muscle cell-mineralocorticoid receptor. Finally, the degree of pulmonary perivascular inflammation was attenuated by mineralocorticoid receptor antagonism and was fully reproduced by smooth muscle cell-specific mineralocorticoid receptor deletion. These studies demonstrate that in the sugen/hypoxia pulmonary hypertension model, systemic-mineralocorticoid receptor blockade significantly attenuates the disease and that mineralocorticoid receptor has cell-specific effects, with endothelial cell-mineralocorticoid receptor contributing to right ventricular perivascular fibrosis and smooth muscle cell-mineralocorticoid receptor participating in pulmonary vascular inflammation. As mineralocorticoid receptor antagonists are being investigated to treat pulmonary arterial hypertension, these findings support novel mechanisms and potential mineralocorticoid receptor targets that mediate therapeutic benefits in patients.
RESUMO
BACKGROUND: Right ventricular function (RVF) is an independent predictor of prognosis for patients undergoing aortic valve replacement: transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). The effect of transfemoral aortic valve replacement (TF-TAVR) on RVF is uncertain. We aimed to perform a meta-analysis of the effect of TF-TAVR on RVF in patients with aortic stenosis (AS) and compare the effect of TF-TAVR with SAVR. METHODS: We searched relevant studies from PubMed, Embase, Cochrane Library databases, and Web of Science. Furthermore, two reviewers (Wang AQ and Cao YS) extracted all relevant data, which were then double checked by another two reviewers (Zhang M and Qi GM). We used the forest plot to present results. Tricuspid annular plane systolic excursion (TAPSE) was the primary outcome. RESULTS: This meta-analysis included 11 studies. There were 353 patients who underwent TF-TAVR, and 358 patients who were subjected to SAVR. There was no significant difference in TAPSE at 1 week and 6 months as well as right ventricular ejection fraction (RVEF) at <2 weeks and 6 months after TF-TAVR. For the SAVR group, TAPSE at 1 week and 3 months as well as fractional area change (FAC) at 3 months post procedure were significantly aggravated, while RVEF did not change significantly. Moreover, TAPSE post-TF-TAVR was significantly improved as compared with post-SAVR. The â³TAPSE, the difference between TAPSE post-procedure and TAPSE prior to procedure, was also significantly better in the TF-TAVR group than in the SAVR group. CONCLUSION: RVF was maintained post TF-TAVR. For SAVR, discrepancy in the measured parameters exists, as reduced TAPSE indicates compromised longitudinal RVF, while insignificant changes in RVEF implicate maintained RVF post procedure. Collectively, our study suggests that the baseline RV dysfunction and the effect of TF-TAVR versus SAVR on longitudinal RVF may influence the selection of aortic valve intervention.
RESUMO
Fibrosing mediastinitis (FM) is a very rare disease, often caused by histoplasmosis capsulatum, tuberculosis, sarcoidosis, autoimmunity and other diseases, such as IgG 4-related diseases. Fibrous structures in the mediastinum compress the pulmonary artery, pulmonary vein, superior vena cava, esophagus, trachea and cardiac vessels, leading to clinical symptoms. Drug therapeutic modality for pulmonary vein stenosis (PVS) caused by FM is palliative in essence and with limited efficacy, whereas surgical treatment causes high mortality. In recent years, catheter-based treatment to FM-caused PVS has emerged as a promising therapeutic modality, however, the safety and effectiveness of this modality remain unclear. Therefore, a systematic review on the safety and efficacy of the catheter-based treatment for PVS caused by FM was performed, in the hope to shed lights on the alternative therapeutic strategy to this fatal disease.
RESUMO
Low-density lipoprotein cholesterol (LDL-C) has been associated with the occurrence of abdominal aortic aneurysm. However, whether LDL-C elevation associated with aneurysms in large vessel vasculitis is unknown. The aim of this study is to investigate the clinical and laboratory features of Takayasu arteritis (TAK) and explore the risk factors that associated with aneurysm in these patients. This retrospective study compared the clinical manifestations, laboratory parameters, and imaging results of 103 TAK patients with or without aneurysms and analyzed the risk factors of aneurysm formation. 20.4% of TAK patients were found to have aneurysms. The LDL-C levels was higher in the aneurysm group than in the non-aneurysm group (2.9 ± 0.9 mmol/l vs. 2.4 ± 0.9 mmol/l, p = 0.032). Elevated serum LDL-C levels increased the risk of aneurysm by 5.8-fold (p = 0.021, odds ratio [OR] = 5.767, 95% confidence interval [CI]: 1.302-25.543), and the cutoff value of level of serum LDL-C was 3.08 mmol/l. The risk of aneurysm was 4.2-fold higher in patients with disease duration >5 years (p = 0.042, OR = 4.237, 95% CI: 1.055-17.023), and 2.9-fold higher when an elevated erythrocyte sedimentation rate was present (p = 0.077, OR = 2.851, 95% CI: 0.891-9.115). In this study, elevated LDL-C levels increased the risk of developing aneurysms in patients with TAK.
Assuntos
Aneurisma/etiologia , Dislipidemias/complicações , Arterite de Takayasu/complicações , Adulto , Aneurisma/diagnóstico por imagem , Aneurisma Aórtico/etiologia , LDL-Colesterol/sangue , Angiografia por Tomografia Computadorizada , Estudos Transversais , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Arterite de Takayasu/diagnóstico por imagem , Fatores de Tempo , Adulto JovemRESUMO
Although studies using animal models have demonstrated that nonhemodynamic factors, including inflammatory cells and cytokines, contribute to left ventricular hypertrophy (LVH), there is little clinical data to confirm this association. Therefore in the present study, levels of circulating specific types of leukocyte were measured to determine the association between white blood cells and left ventricular mass index (LVMI) in hypertensive patients undergoing anti-hypertensive drug therapy. A total of 144 consecutive hypertensive patients taking anti-hypertensive drug therapy were enrolled in the current study. Subjects were divided into two groups: Those with normal geometry and those with left LVH. Total white blood cells and differentiated subtypes (neutrophils, lymphocytes, monocytes) were counted, and left ventricular end-diastolic diameter, left ventricular posterior wall thickness in diastole and inter-ventricular septal wall thickness in diastole were all measured. Analysis revealed a significant correlation between LVMI and total white blood cell levels (P=0.013). The percentage of LVH in the highest tertile of WBC was increased compared with the middle tertile (P=0.008). Furthermore, a significant correlation between the highest tertile of neutrophil counts and LVH was observed (P=0.039). However, no significant associations between LVMI and monocyte or lymphocyte counts were detected. Therefore, the current study determined that increased total white blood cell and neutrophil subtype counts were associated with LVMI in hypertensive patients undergoing anti-hypertensive drug therapy. They may provide convenient and useful markers for further risk appraisal of LVH caused by nonhemodynamic factors of hypertension.