scholarly journals Cell-Specific Dual Role of Caveolin-1 in Pulmonary Hypertension

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Rajamma Mathew
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Dual Role ◽  
Scaffolding Protein ◽  
Suppressor Factor ◽  
Caveolin 1 ◽  
Enhanced Expression

A wide variety of cardiopulmonary and systemic diseases are known to lead to pulmonary hypertension (PH). A number of signaling pathways have been implicated in PH; however, the precise mechanism/s leading to PH is not yet clearly understood. Caveolin-1, a membrane scaffolding protein found in a number of cells including endothelial and smooth muscle cells, has been implicated in PH. Loss of endothelial caveolin-1 is reported in clinical and experimental forms of PH. Caveolin-1, also known as a tumor-suppressor factor, interacts with a number of transducing molecules that reside in or are recruited to caveolae, and it inhibits cell proliferative pathways. Not surprisingly, the rescue of endothelial caveolin-1 has been found not only to inhibit the activation of proliferative pathways but also to attenuate PH. Recently, it has emerged that during the progression of PH, enhanced expression of caveolin-1 occurs in smooth muscle cells, where it facilitates cell proliferation, thus contributing to worsening of the disease. This paper summarizes the cell-specific dual role of caveolin-1 in PH.

Crucial Role of ROCK2 in Vascular Smooth Muscle Cells in Hypoxia-induced Pulmonary Hypertension in Mice

2012 ◽  
Vol 18 (10) ◽  
pp. S189
Author(s):  
Toru Shimizu ◽  
Shin-ichi Tanaka ◽  
Kimio Satoh ◽  
Yoshihiro Fukumoto ◽  
Hiroaki Shimokawa
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Crucial Role ◽  
Muscle Cells

Up-regulation of nPKC Contributes to Proliferation of Pulmonary Artery Smooth Muscle Cells in Hypoxia-induced Pulmonary Hypertension

2020 ◽  
Author(s):  
Yiwei Shi ◽  
Rui Jiang ◽  
Xiaojiang Qin ◽  
Anqi Gao ◽  
Xiaomin Hou ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Smooth Muscle Cells ◽  
Magnetic Separation ◽  
Muscle Cells ◽  
Molecular Therapy ◽  
Different Types ◽  
Pulmonary Artery Smooth Muscle

Abstract Background It has been indicated that protein kinase C (PKC) plays a vital role in the pathogenesis of hypoxia-induced pulmonary hypertension (PH). The functions or the pathogenic roles of PKCs vary from different types, and their related downstream pathways may also be distinct. Therefore, the specific role of different types of PKC deserves to be elucidated. Discussions regarding conventional PKC (cPKC) have dominated research in recent years, however, the relationship between novel PKC (nPKC) and the development of PH remain unclear. In addition, it is less known whether nPKC has a direct effect on the proliferation of pulmonary artery smooth muscle cells (PASMCs). This study is designed to investigate the role of nPKC in mediating PASMCs proliferation in PH and the underlying mechanisms. Methods Mouse PASMCs was isolated using magnetic separation technology. The PASMCs were divided into 24 h group, 48 h group and 72 h group according to different hypoxia treatment time, then detected cell proliferation rate and nPKC expression level in each group. We treated PASMCs with agonists or inhibitors of PKCδ and PKCε and exposed them to hypoxia or normoxia for 72 h, then measured the proliferation of PASMCs. We also constructed a lentiviral vector containing siRNA fragments for inhibiting PKCδ and PKCε to transfected PASMCs, then examined their proliferation. Results PASMCs isolated successfully by magnetic separation method and were in good condition. Hypoxia promoted the proliferation of PASMCs, and the treatment for 72 h had the most significant effect. Hypoxia upregulated the expression of PKCδ and PKCε in mouse PASMCs, leading to PASMCs proliferation. Moreover, Our study demonstrated that hypoxia induced upregulation of PKCδ and PKCε expression resulting to the proliferation of PASMCs via up-regulating the phosphorylation of AKT and ERK. Conclusions Our study provides clear evidence that increased nPKC expression contributes to PASMCs proliferation and uncovers the correlation between AKT and ERK pathways and nPKC-mediated proliferation of PASMCs. These findings may provide novel targets for molecular therapy of pulmonary hypertension.

Abstract 235: Plasma Levels of Cyclophilin A Correlate with Circulating Inflammatory Cytokines in Patients with Pulmonary Hypertension

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Tomohiro Otsuki ◽  
Kimio Satoh ◽  
Nobuhiro Kikuchi ◽  
Junichi Omura ◽  
Shun Kudo ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Growth Factors ◽  
Smooth Muscle Cells ◽  
Inflammatory Cytokines ◽  
Plasma Levels ◽  
Cyclophilin A ◽  
Muscle Cells ◽  
Circulating Cytokines

Background: Excessive proliferation and resistance to apoptosis of pulmonary artery smooth muscle cells (PASMCs) are key characteristics of pulmonary vascular remodeling in patients with pulmonary hypertension (PH). The mechanisms of pathophysiological changes in PH are not fully investigated. Cyclophilin A (CyPA) is secreted from vascular smooth muscle cells (VSMCs) in response to several stimuli, including oxidative stress, mechanical stretch and hypoxia. Extracellular CyPA and its receptor Basigin induce secretion of growth factors and inflammatory cytokines from VSMCs. Additionally, plasma CyPA levels predict poor outcome in patients with PH. In this study, we examined the correlations between plasma CyPA levels and circulating cytokines/chemokines and growth factors in PH patients. Methods and Results: In consecutive 176 patients undergoing right heart catheterization, we examined the relationship between plasma CyPA and inflammatory cytokines/chemokines and growth factors. We used ELISA for CyPA measurement and Bio-Plex system for measurement of inflammatory cytokines/chemokines and growth factors. Plasma CyPA levels in PH patients increased according to their severity assessed by pulmonary vascular resistance (P<0.001). A positive correlation was noted between plasma CyPA levels and several inflammatory cytokines/chemokines and growth factors, including CXCL1 (P<0.001), CXCL9 (P=0.001), macrophage colony-stimulating factor (P=0.020), SDF-1α (P=0.005) and PDGF-BB (P=0.003). Interestingly, there was a significant correlation between plasma levels of CyPA and those of LDL-cholesterol (P=0.003) or HbA1c (P=0.006). In contrast, there was no correlation between CyPA and high-sensitivity CRP (P=0.172). Finally, plasma levels of CyPA and SDF-1α were significantly less in patients with statins (both P<0.01). Conclusions: Plasma levels of CyPA are correlated with those of circulating cytokines/chemokines and growth factors, suggesting an inflammatory role of CyPA in PH patients. These data further support the crucial role of CyPA as a pathogenic molecule and a therapeutic target in PH.

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