Aldosterone Contributed to Pulmonary Arterial Hypertension Development via Stimulating Aquaporin Expression and Pulmonary Arterial Smooth Muscle Cells Proliferation

Pharmacology ◽  
2020 ◽  
Vol 105 (7-8) ◽  
pp. 405-415 ◽  
Author(s):  
Yue Wang ◽  
Bin Zhong ◽  
Qiyong Wu ◽  
Tao Zhu ◽  
Yong Wang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Arterial Smooth Muscle ◽  
Pulmonary Arterial ◽  
Arterial Smooth Muscle Cells ◽  
Pulmonary Arterial Smooth Muscle ◽  
Hypertension Development

scholarly journals Vital Roles of Gremlin‐1 in Pulmonary Arterial Hypertension Induced by Systemic‐to‐Pulmonary Shunts

2020 ◽  
Vol 9 (15) ◽  
Author(s):  
Liukun Meng ◽  
Xiao Teng ◽  
Yao Liu ◽  
Chao Yang ◽  
Shengwei Wang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Arterial Smooth Muscle ◽  
Pulmonary Arterial ◽  
Arterial Smooth Muscle Cells ◽  
Pulmonary Arterial Smooth Muscle ◽  
Gremlin 1

Background Heterozygous mutation in BMP (bone morphogenetic protein) receptor 2 is rare, but BMP cascade suppression is common in congenital heart disease–associated pulmonary arterial hypertension (CHD‐PAH); however, the underling mechanism of BMP cascade suppression independent of BMP receptor 2 mutation is unknown. Methods and Results Pulmonary hypertensive status observed in CHD‐PAH was surgically reproduced in rats. Gremlin‐1 expression was increased, but BMP cascade was suppressed, in lungs from CHD‐PAH patients and shunted rats, whereas shunt correction retarded these trends in rats. Immunostaining demonstrated increased gremlin‐1 was mainly in the endothelium and media of remodeled pulmonary arteries. However, mechanical stretch time‐ and amplitude‐dependently stimulated gremlin‐1 secretion and suppressed BMP cascade in distal pulmonary arterial smooth muscle cells from healthy rats. Under static condition, gremlin‐1 significantly promoted the proliferation and inhibited the apoptosis of distal pulmonary arterial smooth muscle cells from healthy rats via BMP cascade. Furthermore, plasma gremlin‐1 closely correlated with hemodynamic parameters in CHD‐PAH patients and shunted rats. Conclusions Serving as an endogenous antagonist of BMP cascade, the increase of gremlin‐1 in CHD‐PAH may present a reasonable mechanism explanation for BMP cascade suppression independent of BMP receptor 2 mutation.

scholarly journals PDGF enhances store-operated Ca2+ entry by upregulating STIM1/Orai1 via activation of Akt/mTOR in human pulmonary arterial smooth muscle cells

2012 ◽  
Vol 302 (2) ◽  
pp. C405-C411 ◽  
Author(s):  
Aiko Ogawa ◽  
Amy L. Firth ◽  
Kimberly A. Smith ◽  
Mary V. Maliakal ◽  
Jason X.-J. Yuan
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Arterial Smooth Muscle ◽  
Pulmonary Arterial ◽  
Arterial Smooth Muscle Cells ◽  
Pulmonary Arterial Smooth Muscle

Platelet-derived growth factor (PDGF) and its receptor are known to be substantially elevated in lung tissues and pulmonary arterial smooth muscle cells (PASMC) isolated from patients and animals with pulmonary arterial hypertension. PDGF has been shown to phosphorylate and activate Akt and mammalian target of rapamycin (mTOR) in PASMC. In this study, we investigated the role of PDGF-mediated activation of Akt signaling in the regulation of cytosolic Ca2+ concentration and cell proliferation. PDGF activated the Akt/mTOR pathway and, subsequently, enhanced store-operated Ca2+ entry (SOCE) and cell proliferation in human PASMC. Inhibition of Akt attenuated the increase in cytosolic Ca2+ concentration due to both SOCE and PASMC proliferation. This effect correlated with a significant downregulation of stromal interacting molecule (STIM) and Orai, proposed molecular correlates for SOCE in many cell types. The data from this study present a novel pathway for the regulation of Ca2+ signaling and PASMC proliferation involving activation of Akt in response to upregulated expression of PDGF. Targeting this pathway may lead to the development of a novel therapeutic option for the treatment of pulmonary arterial hypertension.

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