Exogenous nerve growth factor supplementation elevates myocardial immunoreactivity and attenuates cardiac remodeling in pressure-overload rats

• Published in: Acta biochimica et biophysica Sinica Vol. 44; no. 11; pp. 931 - 938
• Main Authors: He, Bing, Ye, Fan, Zhou, Xin, Li, He, Xun, Xiaoqing, Ma, Xiaoqing, Liu, Xudong, Wang, Zhihong, Xu, Pengxiao, Li, Yuming
• Format: Journal Article
• Language: English
• Published: China 01.11.2012
• Subjects: Animals; Base Sequence; Blotting, Western; DNA Primers; Heart - drug effects; Immunohistochemistry; Male; Nerve Growth Factor - administration & dosage; Nerve Growth Factor - pharmacology; NGF受体; p75NTR; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; RNA, Messenger - genetics; 免疫反应性; 外源性; 大鼠; 心肌重塑; 神经生长因子; 超负荷
• ISSN: 1672-9145; 1745-7270
• DOI: 10.1093/abbs/gms082

It is postulated that supplementation of exogenous nerve growth factor （NGF） might mediate improvement of the cardiac sympathetic nerve function in heart failure （HF）. Local intramuscular injection of NGF near the cardiac sympathetic ganglia could influence the innervation pattern, norepinephrine transporter （NET） gene expres- sion, and improve the cardiac remodeling in experimental HF animals. In this study, we injected NGF into the sca- lenus medius muscles of Sprague-Dawiey rats with ab- dominal aortic constriction （AC）. The nerve innervated pattern, left ventricular morphology, and function follow- ing injection in rats with AC were investigated respectively by immunohistochemistry and echocardiography. Levels of mRNA expression of NET, growth associated protein 43 （GAP 43）, NGF and its receptors TrkA and p75NTR, and brain natriuretic peptide （BNP） were measured by real- time polymerase chain reaction. The results showed that myocardial NGF mRNA levels were comparable in rats with AC. Short-term supplementation of exogenous NGF raised the myocardial NGF immunoreactivity, but did not cause hyperinnervation and NET mRNA upregulation in the AC rats. Furthermore, myocardial TrkA mRNA was found to be remarkably decreased and p75NTR mRNA was increased. Myocardial TrkA downregulation may play a beneficial effect for avoiding the hyperinnervation, and it is reasonable to postulate that p75NTR can function as an NGF receptor in the absence of TrkA. Interestingly, local NGF administration into the neck muscles near the ganglia could attenuate cardiac remodeling and downre- gulate BNP mRNA. These results suggest that exogenous NGF can reach the target tissue along the axons antero- gradely, and improve the cardiac remodeling.