Aucubin Protects against Myocardial Infarction-Induced Cardiac Remodeling via nNOS/NO-Regulated Oxidative Stress.
Zheng YangQing-Qing WuYang XiaoMing Xia DuanChen LiuYuan YuanYan-Yan MengHai Han LiaoQi-Zhu TangPublished in: Oxidative medicine and cellular longevity (2018)
Whether aucubin could protect myocardial infarction- (MI-) induced cardiac remodeling is not clear. In this study, in a mouse model, cardiac remodeling was induced by left anterior descending coronary artery ligation surgery. Mice were intraperitoneally injected with aucubin (10 mg/kg) 3 days post-MI. Two weeks post-MI, mice in the aucubin treatment group showed decreased mortality, decreased infarct size, and improved cardiac function. Aucubin also decreased cardiac remodeling post-MI. Consistently, aucubin protected cardiomyocytes against hypoxic injury in vitro. Mechanistically, we found that aucubin inhibited the ASK1/JNK signaling. These effects were abolished by the JNK activator. Moreover, we found that the oxidative stress was attenuated in both in vivo aucubin-treated mice heart and in vitro-treated cardiomyocytes, which caused decreased thioredoxin (Trx) consumption, leading to ASK1 forming the inactive complex with Trx. Aucubin increased nNOS-derived NO production in vivo and vitro. The protective effects of aucubin were reversed by the NOS inhibitors L-NAME and L-VINO in vitro. Furthermore, nNOS knockout mice also reversed the protective effects of aucubin on cardiac remodeling. Taken together, aucubin protects against cardiac remodeling post-MI through activation of the nNOS/NO pathway, which subsequently attenuates the ROS production, increases Trx preservation, and leads to inhibition of the ASK1/JNK pathway.
Keyphrases
- left ventricular
- oxidative stress
- coronary artery
- heart failure
- cell death
- high glucose
- induced apoptosis
- cardiovascular disease
- acute myocardial infarction
- cardiovascular events
- coronary artery disease
- nitric oxide
- atrial fibrillation
- pulmonary artery
- acute coronary syndrome
- adipose tissue
- skeletal muscle
- coronary artery bypass
- nuclear factor
- gestational age