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OBJECTIVE: Reportedly, nestin was re-expressed in proliferative synthetic-type pulmonary artery smooth muscle cells (PASMCs) and obligatory for PASMC proliferation in pulmonary arterial hypertension (PAH). Accordingly, nestin is increased in pulmonary vascular lesions of congenital heart disease (CHD)-associated PAH patients. We tested the hypothesis whether nestin was re-expressed in proliferative synthetic-type PASMCs and associated with pulmonary vascular remodeling in CHD-PAH. MATERIALS AND METHODS: Nestin expression was tested using lung tissues from CHD-PAH patients and monocrotaline (MCT) plus aortocaval (AV) shunt-induced PAH rats, human PASMCs (HPASMCs), and pulmonary artery endothelial cells (PAECs) and PASMCs from MCT-AV-induced PAH rats. The role and possible mechanism of nestin on HPASMC proliferation, apoptosis, cell cycle and migration were investigated by assays of CCK-8, EdU, TUNEL, flow cytometry, transwell chamber and immunoblotting assays. RESULTS: Nestin was solely expressed in proliferative synthetic-type PASMCs, but rarely detected in PAECs. Nestin was barely detected in normal pulmonary arterioles and occlusive pulmonary vascular lesions. Its expression was robustly increased in developing pulmonary vasculature, but returned to normal levels at the late stage of pulmonary vascular remodeling in lung tissues from CHD-PAH patients and MCT-AV-induced PAH rats. Besides, nestin peaks were consistent with the histological features in lung tissues of MCT-AV-induced PAH rats. Moreover, nestin overexpression effectively promoted HPASMC phenotypic transformation, proliferation, apoptosis resistance and migration via enhancing Wnt/ß-catenin activation. CONCLUSIONS: These data indicated that nestin was re-expressed in proliferative synthetic-type PASMCs and might represent a potential marker of pulmonary vascular remodeling in CHD-PAH.
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Cardiopatias Congênitas/metabolismo , Cardiopatias Congênitas/fisiopatologia , Pulmão/fisiopatologia , Nestina/metabolismo , Hipertensão Arterial Pulmonar/metabolismo , Hipertensão Arterial Pulmonar/fisiopatologia , Remodelação Vascular , Adolescente , Adulto , Idoso , Animais , Biomarcadores/metabolismo , Criança , Pré-Escolar , Células Endoteliais/metabolismo , Feminino , Cardiopatias Congênitas/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Monocrotalina , Miócitos de Músculo Liso/metabolismo , Fenótipo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Hipertensão Arterial Pulmonar/complicações , Artéria Pulmonar/patologia , Ratos Sprague-Dawley , Fatores de Tempo , Via de Sinalização Wnt , Adulto JovemRESUMO
Background: Pulmonary arterial hypertension (PAH) leads to myocardial remodeling, manifesting as mechanical dyssynchrony (M-dys) and electrical dyssynchrony (E-dys), in both right (RV) and left ventricles (LV). However, the impacts of layer-specific intraventricular M-dys on biventricular functions and its association with E-dys in PAH remain unclear. Methods: Seventy-nine newly diagnosed patients with PAH undergoing cardiac magnetic resonance scanning were consecutively recruited between January 2011 and December 2017. The biventricular volumetric and layer-specific intraventricular M-dys were analyzed. The QRS duration z-scores were calculated after adjusting for age and sex. Results: 77.22 % of patients were female (mean age 30.30 ± 9.79 years; median follow-up 5.53 years). Further, 29 (36.71 %) patients succumbed to all-cause mortality by the end of the study. At the baseline, LV layer-specific intraventricular M-dys had apparent transmural gradients compared with RV in the radial and circumferential directions. However, deceased patients lost the transmural gradients. The LV longitudinal strain rate time to late diastolic peak in the myocardial region (LVmyoLSRTTLDPintra) predicted long-term survival. The Kaplan-Meier curve revealed that patients with PAH with LVmyoLSRTTLDPintra <20.01 milliseconds had a worse prognosis. Larger right ventricle (RV) intraventricular M-dys resulted in worse RV ejection fraction. However, larger LV intraventricular M-dys in the late diastolic phase indicated remarkable exercise capacity and higher LV stroke volume index. E-dys and intraventricular M-dys had no direct correlations. Conclusions: The layer-specific intraventricular M-dys had varying impacts on biventricular functions in PAH. PAH patients with LVmyoLSRTTLDPintra <20.01 milliseconds had a worse prognosis. LV intraventricular M-dys in the late diastolic phase needs more attention to precisely evaluate LV function.
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PURPOSE: To investigate the imaging characteristics and prognostic factors for the long-term survival of Behcet's disease (BD) with arterial involvement. METHODS: In this retrospective study, BD patients with arterial involvement were identified from January 2003 to January 2020. Arterial lesions were detected by ultrasonography, traditional arteriography, and/or computed tomography angiography (CTA). Cox proportional hazards regression analyses were performed to identify the prognostic factors. RESULTS: Totally, 84 BD patients with arterial involvement were identified (73.8 % males). The mean age at BD diagnosis was 39.1 ± 13.1 years. Arterial involvement was the initial manifestation in 33.3 % of the patients, and the median time from BD diagnosis to arterial involvement was 6 (IQR 1-15.5) years for the rest of patients. Systemic artery involvement and pulmonary artery involvement (PAI) were found in 64 and 27 patients, respectively. Approximately 94.0 % (79/84) of the patients had more than one artery involved concurrently or successively during the course of BD. Aneurysm/dilation was the most prevalent lesion in the aorta (76.0 %), while stenosis/occlusion was the main lesion of the coronary artery (90.9 %) and other aortic branches (74.5 %). Pulmonary hypertension was found in 70.4 % (19/27) of patients with PAI. The 5- and 10-year survival rates of BD patients with arterial involvement were 87.4 % and 84.1 %, respectively. Cardiac involvement (HR: 4.34) and pulmonary artery aneurysm/dilation (HR: 4.89) were independently associated with mortality. CONCLUSIONS: Arterial lesions associated with BD usually involve multiple arteries and manifest differently in different types of arteries. Cardiac involvement and pulmonary artery aneurysm/dilation are independent prognostic factors of BD patients with arterial involvement.
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Aneurisma , Síndrome de Behçet , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , Síndrome de Behçet/diagnóstico por imagem , Seguimentos , Estudos Retrospectivos , Prognóstico , Artéria Pulmonar/diagnóstico por imagemRESUMO
Right heart thrombus (RHT) is a rare but life-threatening condition in acute pulmonary embolism (APE) without clear management guidelines. This study aimed to address the clinical characteristics and outcomes of RHT-APE in Chinese patients. In this study, 17 RHT-APE and 329 non-RHT-APE patients, who were diagnosed between September 2015 and August 2019, were retrospectively recruited with the median follow-up was 360 days. The overall prevalence of RHT was 4.91% in APE. Its prevalence increased along the increase of APE risk stratifications. Comparisons showed that with higher proportion of male gender and younger age, RHT-APE patients also had worse hemodynamic instability and heart function, and higher risk stratification levels than non-RHT-APE patients. After adjusting by age and gender, multivariate logistic regression analysis found high/intermediate-high risk stratification, decreased right ventricular (RV) motion, NT-proBNP >600 pg/mL, and RV dysfunction were risk factors for RHT. Kaplan-Meier analysis showed non-RHT had better prognosis than RHT patients (30-day survival: log-rank: p < 0.001; 90-day survival: log-rank: p = 0.002). The multivariate logistic regression analysis showed RHT was an independent risk factor for 30-day mortality in APE. The subgroup analysis showed RHT would result in worse outcomes in patients who already had higher APE early mortality risk. RHT would increase the risk of 30- and 90-day mortality in APE. More attention should be paid to young male APE patients with decreased RV motion, NT-proBNP >600 pg/mL, RV dysfunction, or high level of risk stratification, to exclude the coexistence of RHT.
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AIMS: Orchestrating the transition from reversible medial hypertrophy to irreversible plexiform lesions is crucial for pulmonary arterial hypertension related to congenital heart disease (CHD-PAH). Transgelin is an actin-binding protein that modulates pulmonary arterial smooth muscle cell (PASMC) dysfunction. In this study, we aimed to probe the molecular mechanism and biological function of transgelin in the pathogenesis of CHD-PAH. METHODS AND RESULTS: Transgelin expression was detected in lung tissues from both CHD-PAH patients and monocrotaline (MCT)-plus aortocaval (AV)-induced PAH rats by immunohistochemistry. In vitro, the effects of transgelin on the proliferation, migration, and apoptosis of human PASMCs (HPASMCs) were evaluated by the cell count and EdU assays, transwell migration assay, and TUNEL assay, respectively. And the effect of transgelin on the expression of HPASMC phenotype markers was assessed by the immunoblotting assay. (i) Compared with the normal control group (n = 12), transgelin expression was significantly overexpressed in the pulmonary arterioles of the reversible (n = 15) and irreversible CHD-PAH group (n = 4) (reversible group vs. control group: 18.2 ± 5.1 vs. 13.6 ± 2.6%, P < 0.05; irreversible group vs. control group: 29.9 ± 4.7 vs. 13.6 ± 2.6%, P < 0.001; irreversible group vs. reversible group: 29.9 ± 4.7 vs. 18.2 ± 5.1, P < 0.001). This result was further confirmed in MCT-AV-induced PAH rats. Besides, the transgelin expression level was positively correlated with the pathological grading of pulmonary arteries in CHD-PAH patients (r = 0.48, P = 0.03, n = 19). (ii) Compared with the normal control group (n = 12), TGF-ß1 expression was notably overexpressed in the pulmonary arterioles of the reversible (n = 15) and irreversible CHD-PAH group (n = 4) (reversible group vs. control group: 14.8 ± 4.4 vs. 6.0 ± 2.5%, P < 0.001; irreversible group vs. control group: 20.1 ± 4.4 vs. 6.0 ± 2.5%, P < 0.001; irreversible group vs. reversible group: 20.1 ± 4.4 vs. 14.8 ± 4.4, P < 0.01). The progression-dependent correlation between TGF-ß1 and transgelin was demonstrated in CHD-PAH patients (r = 0.48, P = 0.04, n = 19) and MCT-AV-induced PAH rats, which was further confirmed at sub-cellular levels. (iii) Knockdown of transgelin diminished proliferation, migration, apoptosis resistance, and phenotypic transformation of HPASMCs through repressing the TGF-ß1 signalling pathway. On the contrary, transgelin overexpression resulted in the opposite effects. CONCLUSIONS: These results indicate that transgelin may be an indicator of CHD-PAH development via boosting HPASMC dysfunction through positive regulation of the TGF-ß1 signalling pathway, as well as a potential therapeutic target for the treatment of CHD-PAH.
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Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Animais , Humanos , Ratos , Proliferação de Células/genética , Hipertensão Pulmonar/etiologia , Proteínas dos Microfilamentos/metabolismo , Monocrotalina/metabolismo , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Hipertensão Arterial Pulmonar/etiologia , Artéria Pulmonar , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Asthma is a chronic inflammatory disease of the airways in which many cells are involved, including mast cells, eosinophils, T lymphocytes, and so on. During the process, many chemokines and mediators are released to engage in recruiting and activating eosinophils and other inflammatory cells. Also, some signaling pathways are involved in the pathobiology of asthma. Sonic hedgehog (Shh) is one of the members of hedgehog gene families. Shh signaling plays a critical role in the embryonic development, including the lung. Previous findings from our team reveal that Shh is involved in the asthma pathogenesis. Recombinant Shh could induce the CC chemokine ligand 2 (CCL2) overexpressing and Smo inhibitor GDC-O449 could inhibit CCL2 expression in airway epithelial cells, monocytes, or macrophages. Hence, we reviewed the effects of Shh and CCL2 signaling pathways, and the interaction between signaling pathways in asthma.