Electroacupuncture Preconditioning Improves Myocardial Infarction Injury via Enhancing AMPK-Dependent Autophagy in Rats.

BACKGROUND: Electroacupuncture (EA) pretreatment plays a protective role in myocardial infarction injury. However, the mechanism of electroacupuncture remains unknown. The aim of this study was to confirm the protective effects of electroacupuncture (EA) on myocardial infarction injury and the possible mechanism. METHODS: Sprague-Dawley (SD) rats, used to serve as acute myocardial infarction (AMI) model, were divided into sham group, model (M) group, M+EA group, AMPK inhibitor Compound C (M+EA+CC), and AMPK inhibitor solvent control (M+EA+DMSO) group, respectively. Rats in EA group were pretreated with EA and those in M+EA+CC group with intravenous AMPK inhibitor Compound C. The myocardial morphological changes and infarct size were observed through HE staining and TTC staining, and the concentrations of CK-MB and LDH were detected using ELISA kits. Transmission electron microscopy was employed to observe the autophagosome formation, and the AMPK-dependent autophagy-related protein expression was detected by immunohistochemistry and western blot. RESULTS: EA could alleviate myocardial infarction injury and decrease the concentrations of CK-MB and LDH. Transmission electron microscopy showed that EA could also regulate the AMPK-dependent autophagosome formation and the AMPK-dependent autophagy-related protein expression. AMPK inhibitor Compound C could impair the effect of EA through regulating the concentrations of CK-MB and LDH, autophagosome formation, and autophagy-related protein expression. CONCLUSION: These results indicated that electroacupuncture could improve myocardial infarction injury and induce autophagy, and AMPK-dependent autophagy might be involved in this process.

Electrical remodelling precedes heart failure in an endothelin-1-induced model of cardiomyopathy.

AIMS: Binary transgenic (BT) mice with doxycycline (DOX)-suppressible cardiac-specific overexpression of endothelin-1 (ET-1) exhibit progressive heart failure (HF), QRS prolongation, and death following DOX withdrawal. However, the molecular basis and reversibility of the electrophysiological abnormalities in this model were not known. Here, we assess the mechanisms underlying ET-1-mediated electrical remodelling, and its role in HF. METHODS AND RESULTS: BT vs. non-BT littermate controls were withdrawn from DOX and serially studied with ultrasound biomicroscopy, octapolar catheters, multielectrode epicardial mapping, histopathology, western blot, immunohistochemistry, and qRT-PCR. Abnormalities in ventricular activation and -dV/dt were detected as early as 4 weeks after transgene activation, when the structure and function of the heart remained unaffected. By 8 weeks of ET-1 overexpression, biventricular systolic and diastolic dysfunction, myocardial fibrosis, and cardiomyocyte hypertrophy were observed. Intracardiac and epicardial electrograms revealed prolonged conduction and ventricular activation, reduced -dV/dt, and abnormal atrioventricular nodal function. Within 4 weeks of ET-1 induction, connexin 40 (Cx40) protein and Cx43 mRNA, protein, and phosphorylation levels were reduced by 36, 64, 93, and 69%, respectively; Na(v)1.5 mRNA and protein levels were reduced by 30 and 50%, respectively, as was Na(+) channel conductance. Importantly, the associated electrophysiological abnormalities at this time point were reversible upon suppression of ET-1 overexpression and completely prevented the development of structural and functional remodelling. CONCLUSION: ET-1-mediated electrical remodelling correlates with reduced Cx40, Cx43, and Na(v)1.5 expression and decreased Na(+) channel conductance and precedes HF. The sequence and reversibility of this phenotype suggest that a primary abnormality in electrical remodelling may contribute to the pathogenesis of HF.