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Serotonin and chronic hypoxic pulmonary hypertension activate a NADPH oxidase 4 and TRPM2 dependent pathway for pulmonary arterial smooth muscle cell proliferation and migration
Vascul Pharmacol. 2021 Mar 29:106860. doi: 10.1016/j.vph.2021.106860. Online ahead of print.ABSTRACT5-Hydroxytryptamine (5-HT)-dependent signaling mediated through its transporter and receptors plays important roles in chronic hypoxic pulmonary hypertension (CHPH), which is associated with aberrant reactive oxygen species (ROS) production. NADPH oxidase 4 (NOX4) is one of the major sources of ROS in pulmonary vasculature, and has been implicated in the development of PH. NOX4 generates H2O2, which can activate the transient receptor potential melastatin 2 (TRPM2) channels, providing Ca2+ signals for cell proliferation and ...
Source: Vascular Pharmacology - April 1, 2021 Category: Drugs & Pharmacology Authors: Jia-Lin Song Si-Yi Zheng Rui-Lan He Long-Xin Gui Mo-Jun Lin James S K Sham Source Type: research

Up-regulation of nPKC contributes to proliferation of mice pulmonary artery smooth muscle cells in hypoxia-induced pulmonary hypertension
This study is designed to investigate the role of novel protein kinases C (nPKC) in mediating pulmonary artery smooth muscle cells (PASMCs) proliferation in pulmonary hypertension (PH) and the underlying mechanisms. 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 PKCdelta (PKCδ) and PKCepsilon (PKCε) and exposed them to hypoxia or normoxia for 72 h, then measured the ...
Source: European Journal of Pharmacology - March 22, 2021 Category: Drugs & Pharmacology Authors: Yiwei Shi Rui Jiang Xiaojiang Qin Anqi Gao Xiaomin Hou Liangjing Chen Xinrong Xu Yunting Guo Lina Chai Liangyuan Zhao Xuefeng Du Furong Wu Source Type: research

Tetrahydroxystilbene glycoside improves endothelial dysfunction and hypertension in obese rats: the role of omentin-1
CONCLUSIONS: Down-regulation of omentin-1 induces endothelial dysfunction and hypertension in obesity. TSG treatment (at least partially) increases omentin-1 via promoting binding of PPAR-γ and Itln-1 promoter in adipose tissues, subsequently exerts protective effects on endothelial function via activating Akt/eNOS/NO signaling and attenuating oxidative/nitrative stress. These results suggest that TSG could be developed as a promising anti-hypertension agent that protects against endothelial dysfunction and obesity-associated cardiovascular diseases.PMID:33647262 | DOI:10.1016/j.bcp.2021.114489
Source: Biochemical Pharmacology - March 1, 2021 Category: Drugs & Pharmacology Authors: Qianqian Dong Wenjuan Xing Kaifeng Li Xuanxuan Zhou Siwang Wang Haifeng Zhang Source Type: research

Protective effects of dioscin on vascular remodeling in pulmonary arterial hypertension via adjusting GRB2/ERK/PI3K-AKT signal.
In this study, effect of dioscin on vascular remodeling in PAH was assessed in hypoxia-induced PASMCs, hypoxia-induced and monocrotaline (MCT)-induced rats. Western blot, Real-time PCR and siRNA transfection tests were applied to evaluate the possible mechanisms of dioscin. In vitro experiments, results showed dioscin markedly inhibited the proliferation and migration, and promoted apoptosis of hypoxic PASMCs. In vivo, dioscin significantly decreased the right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI), and improved pulmonary vascular stenosis in rats induced by hypoxia or MCT. Mole...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - January 1, 2021 Category: Drugs & Pharmacology Authors: Yang Y, Yin L, Zhu M, Song S, Sun C, Han X, Xu Y, Zhao Y, Qi Y, Xu L, Peng JY Tags: Biomed Pharmacother Source Type: research

Sphingosine-1-phosphate promotes pulmonary artery smooth muscle cells proliferation by stimulating autophagy-mediated E-cadherin/CDH1 down-regulation.
Abstract It has been shown that sphingosine-1-phosphate (S1P) is elevated in patients with pulmonary arterial hypertension (PAH) and promotes the proliferation of pulmonary artery smooth muscle cells (PASMCs). Meanwhile, S1P has been found to induce the activation of autophagy in several types of human diseases including cancers. However, it is still unclear whether activation of autophagy mediates S1P-induced PASMCs proliferation, and detailed mechanisms responsible for these processes are indefinite. The aims of this study are to address these issues. S1P dose- and time-dependently reduced the expression of E-ca...
Source: European Journal of Pharmacology - July 9, 2020 Category: Drugs & Pharmacology Authors: Zhai C, Feng W, Shi W, Wang J, Zhang Q, Yan X, Wang Q, Li S, Liu L, Pan Y, Zhu Y, Chai L, Li C, Liu P, Chen Y, Li M Tags: Eur J Pharmacol Source Type: research

Knockout of the Circadian Clock Protein PER1 Results in Sex-Dependent Alterations of ET-1 Production in Mice in Response to a High Salt Diet plus Mineralocorticoid Treatment.
Abstract Previously, we showed that global knockout (KO) of the circadian clock transcription factor PER1 in male, but not female, mice fed a high salt diet plus mineralocorticoid treatment (HS/DOCP) resulted in non-dipping hypertension and decreased night/day ratio of sodium (Na) excretion. Additionally, we have shown that the endothelin-1 (ET-1) gene is targeted by both PER1 and aldosterone. We hypothesized that ET-1 would exhibit a sex-specific response to HS/DOCP treatment in PER1 KO. Here we show that male, but not female, global PER1 KO mice exhibit a decreased night/day ratio of urinary ET-1. Gene expressio...
Source: Canadian Journal of Physiology and Pharmacology - May 20, 2020 Category: Drugs & Pharmacology Authors: Douma LG, Crislip GR, Cheng KY, Barral D, Masten S, Holzworth MR, Roig E, Glasford K, Beguiristain K, Li W, Bratanatawira P, Lynch IJ, Cain BD, Wingo CS, Gumz ML Tags: Can J Physiol Pharmacol Source Type: research

Leukotriene B4 induces proliferation of rat pulmonary arterial smooth muscle cells via modulating GSK-3 β/β-catenin pathway.
Leukotriene B4 induces proliferation of rat pulmonary arterial smooth muscle cells via modulating GSK-3β/β-catenin pathway. Eur J Pharmacol. 2019 Nov 23;:172823 Authors: Li S, Zhai C, Shi W, Feng W, Xie X, Pan Y, Wang J, Yan X, Chai L, Wang Q, Zhang Q, Liu P, Li M Abstract Leukotriene B4 (LTB4) has been found to contribute to pulmonary arterial smooth muscle cells (PASMCs) proliferation and pulmonary arterial remodeling therefore the development of pulmonary arterial hypertension (PAH). Yet, the underlying molecular mechanisms remain poorly understood. The present study aims to address this issue. O...
Source: European Journal of Pharmacology - November 22, 2019 Category: Drugs & Pharmacology Authors: Li S, Zhai C, Shi W, Feng W, Xie X, Pan Y, Wang J, Yan X, Chai L, Wang Q, Zhang Q, Liu P, Li M Tags: Eur J Pharmacol Source Type: research

Coordination between NADPH oxidase and vascular peroxidase 1 promotes dysfunctions of endothelial progenitor cells in hypoxia-induced pulmonary hypertensive rats.
This study aims to evaluate the correlation between NOX/VPO1 pathway and endothelial progenitor cells (EPCs) dysfunctions in hypoxia-induced pulmonary hypertension (PH). The rats were exposed to 10% hypoxia for 3 weeks to establish a PH model, which showed increases in right ventricle systolic pressure, right ventricular and pulmonary vascular remodeling, acceleration in apoptosis and impairment in functions of the peripheral blood derived - EPCs (the reduced abilities in adhesion, migration and tube formation), accompanied by up-regulation of NOX (NOX2 and NOX4) and VPO1. Next, normal EPCs were cultured under hypoxia to i...
Source: European Journal of Pharmacology - June 15, 2019 Category: Drugs & Pharmacology Authors: Wang EL, Jia MM, Luo FM, Li T, Peng JJ, Luo XJ, Song FL, Yang JF, Peng J, Liu B Tags: Eur J Pharmacol Source Type: research

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