Grape seed procyanidin extract attenuates hypoxic pulmonary hypertension by inhibiting oxidative stress and pulmonary arterial smooth muscle cells proliferation.
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.
The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China; Department of Anatomy, Qiqihar Medical University, Qiqihar, China.
Haifeng
H
Jin
The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
Mingcheng
M
Liu
The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
Xin
X
Zhang
The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
Jinjin
J
Pan
The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
Jinzhen
J
Han
The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
Yudong
Y
Wang
The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. Electronic address: haixinlei@dlmedu.edu.cn.
Haixin
H
Lei
The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China; Department of Cardiology, The Second Affiliated Hospital, Dalian Medical University Cancer Center, Dalian, China. Electronic address: yanchunding@aliyun.com.
Yanchun
Y
Ding
The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. Electronic address: yuhuiyuan@hotmail.com.
Yuhui
Y
Yuan
D000818:Animals; D000975:Antioxidants / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D019587:Dietary Supplements / Q000009:adverse effects; D015971:Gene Expression Regulation, Enzymologic; D056604:Grape Seed Extract / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D006976:Hypertension, Pulmonary / Q000178:diet therapy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015227:Lipid Peroxidation; D008168:Lung / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D044945:Proanthocyanidins / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D015427:Reperfusion Injury / Q000178:diet therapy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020545:Respiratory Mucosa / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D066253:Vascular Remodeling
D000975:Antioxidants; D015415:Biomarkers; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D044945:Proanthocyanidins; D017382:Reactive Oxygen Species; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat
Grape seed procyanidin extract; Hypoxic pulmonary hypertension; Proliferation; Reactive oxygen species