Cardioprotection of CAPE-oNO2 against myocardial ischemia/reperfusion induced ROS generation via regulating the SIRT1/eNOS/NF-κB 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 Nω-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-α release and collagen deposition of IR rat hearts. They could agitate SIRT1 and eNOS expression, and consequently enhance NO release and suppress NF-κB 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-κB 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-κB pathway.

Luteolin‐mediated Kim‐1/NF‐kB/Nrf2 signaling pathways protects sodium fluoride‐induced hypertension and cardiovascular complications

“…From the results we obtained, NaF toxicity upregulated both NF‐κB and Nrf2 indicating the capacity of NaF to modulate signaling associated with inflammation, oxidative stress and antioxidant response elements (ARE). Oxidative stress has been reported to be a major trigger of NF‐κB signaling . The observed upregulation of Nrf2 was also a confirmation of the significant increase in the activities of renal GRed, GPx, CAT, and SOD in NaF alone signifying adaptive response of these antioxidant enzymes through Nrf2/ARE pathway to NaF toxicity.…”

Chlorogenic acid: A potent molecule that protects cardiomyocytes from TNF‐α–induced injury via inhibiting NF‐κB and JNK signals

“…46 Recent studies demonstrated that NF-κB has cardioprotective effects though repression of apoptotic cell death induced by hypoxia or myocardial injury. [47][48][49] F I G U R E 5 Role of NF-κB in the protective effect of chlorogenic acid against TNF-α injured cardiomyocytes. hiPSC-CMs were treated with QNZ (1 nmol/L) for 4 h or CGA (0.1 μmol/L or 1 μmol/L) for 12 h prior to incubation with TNF-α for 24 h. Then the apoptosis rate of hiPSC-CMs was detected by Annexin V/PI staining, and the quantitative analysis of hiPSC-CMs apoptosis rate is shown (A, B).…”

<p>Dexmedetomidine protects H9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenation-induced intracellular calcium overload and apoptosis through regulating FKBP12.6/RyR2 signaling</p>

“…1,2 Studies identified various molecular and cellular mechanisms involved in the process of myocardial I/R. [3][4][5][6][7] Of these, intracellular calcium [Ca 2+ ]i overload is a critical one that leads to cardiomyocyte apoptosis and cell death. [8][9][10] Dexmedetomidine (DEX) is a highly selective α2-adrenoceptor agonist with sedative, anxiolytic, analgesic, and sympatholytic properties.…”