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.

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

scholarly journals Role of Endogenous Angiotensin II in the Expression of Growth Factors and the Cell Cycle in Vascular Smooth Muscle Cells from SHR

1998 ◽  
Vol 39 (4) ◽  
pp. 561-561 ◽  
Author(s):  
Chikara Satoh ◽  
Noboru Fukuda ◽  
Atsushi Kubo ◽  
Hirobumi Kishioka ◽  
Mari Nakayama ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Smooth Muscle ◽  
Growth Factors ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
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.

Pathophysiology of uterine leiomyomas

1992 ◽  
Vol 70 (5) ◽  
pp. 273-278 ◽  
Author(s):  
Michael Koutsilieris
Keyword(s):  
Smooth Muscle ◽  
Growth Factors ◽  
Smooth Muscle Cells ◽  
Steroid Hormones ◽  
Muscle Cells ◽  
Uterine Leiomyomas ◽  
Sex Steroid ◽  
Growth Substances ◽  
Therapeutic Approaches

Uterine leiomyomas is the most common benign neoplasia in women, one of the most frequent causes of infertility in reproductive years, and the leading cause for hysterectomy. The pathophysiology of uterine leiomyomas is uncertain. Therefore, therapeutic approaches have been primarily empirical. It is now well documented that growth factors control the functional and possibly the histological integrity of several tissues. Recently the presence of growth substances in uterine tissues suggested that the role of sex steroid hormones in the pathophysiology of leiomyomas may be mediated by substances influencing the proliferation of smooth muscle cells and fibroblasts. This report summarizes the data related to the pathophysiology of leiomyomas, which indicate a possible role of growth factors in uterine leiomyomas.Key words: leiomyomas, growth factors, uterus, smooth muscle cells, fibroblasts.

scholarly journals Divergent changes of p53 in pulmonary arterial endothelial and smooth muscle cells involved in the development of pulmonary hypertension

2019 ◽  
Vol 316 (1) ◽  
pp. L216-L228 ◽  
Author(s):  
Ziyi Wang ◽  
Kai Yang ◽  
Qiuyu Zheng ◽  
Chenting Zhang ◽  
Haiyang Tang ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Transient Receptor Potential ◽  
Muscle Cells ◽  
Transient Receptor Potential Channels ◽  
Nuclear Accumulation ◽  
Pulmonary Vascular Disease ◽  
Pulmonary Arterial

The tumor-suppressive role of p53, a transcription factor that regulates the expression of many genes, has been linked to cell cycle arrest, apoptosis, and senescence. The noncanonical function or the pathogenic role of p53 has more recently been implicated in pulmonary vascular disease. We previously reported that rapid nuclear accumulation of hypoxia-inducible factor (HIF)-1α in pulmonary arterial smooth muscle cells (PASMCs) upregulates transient receptor potential channels and enhances Ca2+ entry to increase cytosolic Ca2+ concentration ([Ca2+]cyt). Also, we observed differences in HIF-1α/2α expression in PASMCs and pulmonary arterial endothelial cells (PAECs). Here we report that p53 is increased in PAECs, but decreased in PASMCs, isolated from mice with hypoxia-induced pulmonary hypertension (PH) and rats with monocrotaline (MCT)-induced PH (MCT-PH). The increased p53 in PAECs from rats with MCT-PH is associated with an increased ratio of Bax/Bcl-2, while the decreased p53 in PASMCs is associated with an increased HIF-1α. Furthermore, p53 is downregulated in PASMCs isolated from patients with idiopathic pulmonary arterial hypertension compared with PASMCs from normal subjects. Overexpression of p53 in normal PASMCs inhibits store-operated Ca2+ entry (SOCE) induced by passive depletion of intracellularly stored Ca2+ in the sarcoplasmic reticulum, while downregulation of p53 enhances SOCE. These data indicate that differentially regulated expression of p53 and HIF-1α/2α in PASMCs and PAECs and the cross talk between p53 and HIF-1α/2α in PASMCs and PAECs may play an important role in the development of PH via, at least in part, induction of PAEC apoptosis and PASMC proliferation.

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