Semaphorin 3A attenuates cardiac autonomic disorders and reduces inducible ventricular arrhythmias in rats with experimental myocardial infarction

Abstract

BackgroundTo investigate the effects of semaphorin 3A (sema 3A) on cardiac autonomic regulation and subsequent ventricular arrhythmias (VAs) in post-infarcted hearts.Method and resultsIn order to explore the functions of sema 3A in post-infarcted hearts, lentivirus-Sema 3A-shRNA and negative control vectors were delivered to the peri-infarcted myocardium rats respectively. Meanwhile, recombinant sema 3A and control (0.9 % NaCl solution) were injected intravenously into infarcted rats to test the therapeutic potential of sema 3A. Results indicated that levels of sema 3A were higher in post-infarcted hearts compared with sham rats. However, sema 3A silencing leaded to sympathetic hyperinnervation, increased myocardial norepinephrine (NE) content and inducible VAs. Conversely, the intravenous administration of sema 3A to infarcted rats reduced sympathetic nerve sprouting, improved cardiac autonomic regulation, and decreased the incidence of inducible VAs. However, both infarct size and cardiac function were similar among infarcted hearts.ConclusionsThe upregulation and administration of sema 3A exerted beneficial effects on infarction-induced cardiac autonomic disorders by increasing cardiac electrical stability and reducing VAs. Sema 3A might be a potential therapeutic agent for cardiac autonomic abnormalities induced arrhythmias.

Targeted regulation of sympathetic activity in paraventricular nucleus reduces inducible ventricular arrhythmias in rats after myocardial infarction

“…In the present study, we implanted bilateral stainless steel guide cannulas into the PVN to microinject LY294002. The NE concentration [21] and RNSA [2] were higher in the MI groups than in the control groups, which was consistent with previous studies and suggested enhancement of sympathetic excitability in rats post-MI. Targeted regulation of sympathetic activity by microinjection of LY294002 into the PVN in MI rats ameliorated the peripheral sympathetic excitability.…”

“…The electrophysiological study was performed as reported previously [14,21]. Electrodes and the epicardial surface of the LV meshed together tightly.…”

Class 3 semaphorins in cardiovascular development

“…Cardiac-specific overexpression of Sema3a induces a reduction of sympathetic innervation and transgenic animals display susceptibility to ventricular tachycardia 44 . Accordingly, it has been reported that myocardial overexpression of Sema3a 45 or intravenous administration of recombinant Sema3A protein 46 after infarction in rats can reduce the probability of ventricular tachycardia that frequently is an associated response to injury, as a result of attenuated sympathetic reinnervation. Moreover, a nonsynonymous polymorphism (I334V, rs138694505A>G) in exon 10 of the human SEMA3A gene was associated with unexplained cardiac arrest and ventricular fibrillation; the axon repelling activity SEMA3A I334V appears significantly weaker of that of its wild type counterpart and in the hearts of patients sympathetic nerves invade the subendocardial layer 47 …”

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