Clopidogrel inhibits angiogenesis of gastric ulcer healing via downregulation of vascular endothelial growth factor receptor 2

Journal of the Formosan Medical Association = Taiwan Yi Zhi
Jiing-Chyuan LuoFa-Yauh Lee

Abstract

Although clopidogrel does not cause gastric mucosal injury, it does not prevent peptic ulcer recurrence in high-risk patients. We explored whether clopidogrel delays gastric ulcer healing via inhibiting angiogenesis and to elucidate the possible mechanisms. Gastric ulcers were induced in Sprague Dawley rats, and ulcer healing and angiogenesis of ulcer margin were compared between clopidogrel-treated rats and controls. The expressions of the proangiogenic growth factors and their receptors including basic fibroblast growth factor (bFGF), bFGF receptor (FGFR), vascular endothelial growth factor (VEGF), VEGFR1, VEGFR2, platelet-derived growth factor (PDGF)A, PDGFB, PDGFR A, PDGFR B, and phosphorylated form of mitogenic activated protein kinase pathways over the ulcer margin were compared via western blot and reverse transcription polymerase chain reaction. In vitro, human umbilical vein endothelial cells (HUVECs) were used to elucidate how clopidogrel inhibited growth factors-stimulated HUVEC proliferation. The ulcer sizes were significantly larger and the angiogenesis of ulcer margin was significantly diminished in the clopidogrel (2 and 10 mg/kg/d) treated groups. Ulcer induction markedly increased the expression of phosphorylat...Continue Reading

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Citations

May 9, 2018·Journal of Cardiovascular Pharmacology·Qi LiXiaoxiao Yang
Oct 21, 2016·Oncotarget·Daniela D'ArcangeloAntonio Facchiano
Dec 31, 2020·Drug Design, Development and Therapy·Hailu WuRuihua Shi
Aug 10, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Ya-Ru GePei-Li Wang

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