Protective role of activating PPARγ in advanced glycation end products-induced impairment of coronary artery vasodilation via inhibiting p38 phosphorylation and reactive oxygen species production

• DOI: 10.1016/j.biopha.2022.112641
• Publication Date: 2022-01-17T10:51:34Z
• Authors: Bing Hua; Qingbo Liu; Side Gao; Weiping Li; Hongwei Li
• Keywords: Malondialdehyde

Advanced glycation end products (AGEs) can damage voltage-gated K+ (Kv) channels and attenuate coronary artery vasodilation, but the underlying mechanisms remain unclear. The aim of this study was to investigate role potential mechanism PPARγ in AGEs-induced Kv 1 impairment. We used both primary rat smooth muscle cells (CSMCs) vitro Zucker Diabetic Fatty (ZDF) model vivo. Overexpression Pparg gene by lentivirus vector (LV-Pparg) transfect CSMCs for upregulation PPARγ. 1.2 1.5 currents were measured patch clamp. vascular tone evaluated isometric force measurements. proteins expression Kv1.2 Kv1.5 channel detected western blot. immunofluorescence Oxidative stress markers including superoxide dismutase (SOD), glutathione peroxidase (GPx) malondialdehyde (MDA) enzyme linked immunosorbent assay (ELISA). phosphorylation p38 mitogen-activated protein kinase (MAPK) total intracellular ROS levels fluorescent dye 2',7'- dichlorofluorescein diacetate (DCFDA) a cellular kit. found that activating via LV-Pparg (100 MOI, 5 × 108 TU/mL) prevented AGEs μg/mL) -mediated impairment activity improved reduction CSMCs. Isometric measurements showed pioglitazone (10 mg/kg/d, intragastric administration) blot analysis increased expression, while inhibiting GW9662 intraperitoneal injection) attenuated these effects ZDF rats. Furthermore, overexpression NADPH oxidase activity, which shown as NOX2 p22phox analysis, decreased MDA production SOD GPx activities ELISA, finally led reduce AGEs-mediated production. Moreover, inhibited MAPK, could NOX2, production, treatment with SB203580 μmol/L), MAPK inhibitor, effects. Activating plays protective vasodilation further decrease oxidative induced overproduction.