Effects of neuregulin-1 on autonomic nervous system remodeling post-myocardial infarction in a rat model

Abstract

Sympathetic nerve and vagus nerve remodeling play an important part in cardiac function post-myocardial infarction (MI). Increasing evidence indicates that neuregulin-1 (NRG-1) improves cardiac function following heart failure. Since its impact on cardiac function and neural remodeling post-MI is poorly understood, we aimed to investigate the role of NRG-1 in autonomic nervous system remodeling post-MI. Forty-five Sprague-Dawley rats were equally randomized into three groups: sham (with the left anterior descending coronary artery exposed but without ligation), MI (left anterior descending coronary artery ligation), and MI plus NRG-1 (left anterior descending coronary artery ligation followed by intraperitoneal injection of NRG-1 (10 μg/kg, once daily for 7 days)). At 4 weeks after MI, echocardiography was used to detect the rat cardiac function by measuring the left ventricular end-systolic inner diameter, left ventricular diastolic diameter, left ventricular end-systolic volume, left ventricular end-diastolic volume, left ventricular ejection fraction, and left ventricular fractional shortening. mRNA and protein expression levels of tyrosine hydroxylase, growth associated protein-43 (neuronal specific protein), nerve growth factor, choline acetyltransferase (vagus nerve marker), and vesicular acetylcholine transporter (cardiac vagal nerve fiber marker) in ischemic myocardia were detected by real-time PCR and western blot assay to assess autonomous nervous remodeling. After MI, the rat cardiac function deteriorated significantly, and it was significantly improved after NRG-1 injection. Compared with the MI group, mRNA and protein levels of tyrosine hydroxylase and growth associated protein-43, as well as choline acetyltransferase mRNA level significantly decreased in the MI plus NRG-1 group, while mRNA and protein levels of nerve growth factor and vesicular acetylcholine transporters, as well as choline acetyltransferase protein level slightly decreased. Our results indicate that NRG-1 can improve cardiac function and regulate sympathetic and vagus nerve remodeling post-MI, thus reaching a new balance of the autonomic nervous system to protect the heart from injury.

Keywords

• nerve remodeling; myocardial infarction; neuregulin-1; sympathetic nerve; vagus nerve; animal model; real-time PCR; western blot assay; cardiac function; echocardiography