Cardioprotection of CAPE-oNO₂ against myocardial ischemia/reperfusion induced ROS generation via regulating the SIRT1/eNOS/NF-?B pathway in vivo and in vitro.

ABSTRACT: Caffeic acid phenethyl ester (CAPE) could ameliorate myocardial ischemia/reperfusion injury (MIRI) by various mechanisms, but there hadn't been any reports on that CAPE could regulate silent information regulator 1 (SIRT1) and endothelial nitric oxide synthase (eNOS) to exert cardioprotective effect. The present study aimed to investigate the cardioprotective potential of caffeic acid o-nitro phenethyl ester (CAPE-oNO₂) on MIRI and the possible mechanism based on the positive control of CAPE. The SD rats were subjected to left coronary artery ischemia /reperfusion (IR) and the H9c2 cell cultured in hypoxia/reoxygenation (HR) to induce the MIRI model. Prior to the procedure, vehicle, CAPE or CAPE-oNO₂ were treated in the absence or presence of a SIRT1 inhibitor nicotinamide (NAM) and an eNOS inhibitor N?-nitro-L-arginine methyl ester (L-NAME). In vivo, CAPE and CAPE-oNO₂ conferred a cardioprotective effect as shown by reduced myocardial infarct size, cardiac marker enzymes and structural abnormalities. From immunohistochemical and sirius red staining, above two compounds ameliorated the TNF-? release and collagen deposition of IR rat hearts. They could agitate SIRT1 and eNOS expression, and consequently enhance NO release and suppress NF-?B signaling, to reduce the malondialdehyde content and cell necrosis. In vitro, they could inhibit HR-induced H9c2 cell apoptosis and ROS generation by activating SIRT1/eNOS pathway and inhabiting NF-?B expression. Emphatically, CAPE-oNO₂ presented the stronger cardioprotection than CAPE both in vivo and in vitro. However, NAM and L-NAME eliminated the CAPE-oNO₂-mediated cardioprotection by restraining SIRT1 and eNOS expression, respectively. It suggested that CAPE-oNO₂ ameliorated MIRI by suppressing the oxidative stress, inflammatory response, fibrosis and necrocytosis via the SIRT1/eNOS/NF-?B pathway.

SUBMITTER: Li D 

PROVIDER: S-EPMC5725281 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature