1. Grape seed procyanidin extract attenuates hypoxic pulmonary hypertension by inhibiting oxidative stress and pulmonary arterial smooth muscle cells proliferation.
- Author
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Jin H, Liu M, Zhang X, Pan J, Han J, Wang Y, Lei H, Ding Y, and Yuan Y
- Subjects
- Animals, Antioxidants adverse effects, Antioxidants metabolism, Biomarkers metabolism, Cell Proliferation, Cells, Cultured, Gene Expression Regulation, Enzymologic, Grape Seed Extract adverse effects, Grape Seed Extract metabolism, Hypertension, Pulmonary diet therapy, Hypertension, Pulmonary metabolism, Hypertension, Pulmonary pathology, Lipid Peroxidation, Lung blood supply, Lung metabolism, Lung pathology, Male, Muscle, Smooth, Vascular enzymology, Muscle, Smooth, Vascular pathology, NADPH Oxidase 4, NADPH Oxidases antagonists & inhibitors, NADPH Oxidases genetics, NADPH Oxidases metabolism, Proanthocyanidins adverse effects, Proanthocyanidins metabolism, Pulmonary Artery metabolism, Pulmonary Artery pathology, Random Allocation, Rats, Sprague-Dawley, Reactive Oxygen Species antagonists & inhibitors, Reactive Oxygen Species metabolism, Reperfusion Injury diet therapy, Reperfusion Injury metabolism, Reperfusion Injury pathology, Respiratory Mucosa blood supply, Respiratory Mucosa metabolism, Respiratory Mucosa pathology, Vascular Remodeling, Antioxidants therapeutic use, Dietary Supplements adverse effects, Grape Seed Extract therapeutic use, Hypertension, Pulmonary prevention & control, Muscle, Smooth, Vascular metabolism, Oxidative Stress, Proanthocyanidins therapeutic use, Reperfusion Injury prevention & control
- Abstract
Hypoxia-induced oxidative stress and excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) play important roles in the pathological process of hypoxic pulmonary hypertension (HPH). Grape seed procyanidin extract (GSPE) possesses antioxidant properties and has beneficial effects on the cardiovascular system. However, the effect of GSPE on HPH remains unclear. In this study, adult Sprague-Dawley rats were exposed to intermittent chronic hypoxia for 4 weeks to mimic a severe HPH condition. Hemodynamic and pulmonary pathomorphology data showed that chronic hypoxia significantly increased right ventricular systolic pressures (RVSP), weight of the right ventricle/left ventricle plus septum (RV/LV+S) ratio and median width of pulmonary arteries. GSPE attenuated the elevation of RVSP, RV/LV+S, and reduced the pulmonary vascular structure remodeling. GSPE also increased the levels of SOD and reduced the levels of MDA in hypoxia-induced HPH model. In addition, GSPE suppressed Nox4 mRNA levels, ROS production and PASMCs proliferation. Meanwhile, increased expression of phospho-STAT3, cyclin D1, cyclin D3 and Ki67 in PASMCs caused by hypoxia was down-regulated by GSPE. These results suggested that GSPE might potentially prevent HPH via antioxidant and antiproliferative mechanisms., (Copyright © 2016. Published by Elsevier Inc.)
- Published
- 2016
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