Renal Sympathetic Denervation in Rats Ameliorates Cardiac Dysfunction and Fibrosis Post-Myocardial Infarction Involving MicroRNAs
Xiaoxin Zheng, Xiaoyan Li, Yongnan Lyu, Yiyu He, Weiguo Wan, Xuejun Jiang
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (mainland)
Med Sci Monit 2016; 22:2751-2760
The role of renal sympathetic denervation (RSD) in ameliorating post-myocardial infarction (MI) left ventricular (LV) fibrosis via microRNA-dependent regulation of connective tissue growth factor (CTGF) remains unknown.
MATERIAL AND METHODS: MI and RSD were induced in Sprague–Dawley rats by ligating the left coronary artery and denervating the bilateral renal nerves, respectively. Norepinephrine, renin, angiotensin II and aldosterone in plasma, collagen, microRNA21, microRNA 101a, microRNA 133a and CTGF in heart tissue, as well as cardiac function were evaluated six weeks post-MI.
RESULTS: In the RSD group, parameters of cardiac function were significantly improved as evidenced by increased LV ejection fraction (p<0.01), LV end-systolic diameter (p<0.01), end-diastolic diameter (p<0.05), LV systolic pressure (p<0.05), maximal rate of pressure rise and decline (dP/dtmax and dP/dtmin, p<0.05), and decreased LV end-diastolic pressure (p<0.05) when compared with MI rats. Further, reduced collagen deposition in peri-infarct myocardium was observed in RSD-treated rats along with higher microRNA101a and microRNA133a (p<0.05) and lower microRNA21 expression (p<0.01) than in MI rats. CTGF mRNA and protein levels were decreased in LV following RSD (p<0.01), accompanied by decreased expression of norepinephrine, renin, angiotensin II and aldosterone in plasma (p<0.05) compared with untreated MI rats.
CONCLUSIONS: The potential therapeutic effects of RSD on post-MI LV fibrosis may be partly mediated by inhibition of CTGF expression via upregulation of microRNA 101a and microRNA 133a and downregulation of microRNA21.
Keywords: Fibrosis - therapy, Animals, Heart Ventricles - pathology, Male, MicroRNAs - metabolism, Myocardial Infarction - therapy, Myocardium - pathology, Random Allocation, Rats, Rats, Sprague-Dawley, Sympathectomy - methods, Ventricular Dysfunction, Left - therapy, Ventricular Function, Left, Ventricular Remodeling