YanRong Liu1, Bing Li1, MingHui Li1, YiHui Yu1, ZhiMei Wang1, ShaoLiang Chen2. 1. Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, China. 2. Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, China. Electronic address: chmengx@126.com.
Abstract
AIMS: Insulin resistance (IR) and sympathetic over-activation play a critical role in diabetic cardiomyopathy (DCM). Percutaneous renal sympathetic denervation (RDN) was tested to treat refractory hypertension. However, the benefits of RDN for DCM and IR still remain unknown. The present study aimed to investigate the effect and associated mechanisms of bilateral surgical RDN (bsRDN) on cardiac function and glucose metabolism in animals with diabetes. METHODS: Thirty-two male New Zealand white rabbits were randomly assigned to Chow (n=8, normal diet) and TEST (n=24, high-fructose fat diet [HFD]) groups. At 48 weeks after HFD feeding, animals in the TEST group were randomized to the Sham, HFD, and RDN subgroups and were fed a HFD for an additional 8 weeks. Repeated measurements of cardiac function, IR, apoptosis/autophagy, and histopathological assessment were performed at 48 and 56 weeks. RESULTS: HFD feeding for 56 weeks induced IR and diastolic cardiac dysfunction with hypertrophy in septum but well preserved eject fraction in the animals. Impaired IR further deteriorated over the time in the RDN group, featured by a more profound reduction in GLUT4 mRNA and its translocation to the plasma membrane. Successful denervation was associated with improvement of cardiac function via preventing myocardial fibrosis and over-expression of procollagen III, mammalian target of rapamycin, and cardiac apoptosis. Cardiac autophagy, assessed by either electron microscopy or Western blot, was enhanced by bsRDN. CONCLUSIONS: Renal sympathetic denervation led to a significant improvement of HFD-induced cardiac dysfunction by shifting the cardiac apoptosis to autophagy, but worsening IR. Further study is required to identify the clinical benefits of RDN.
AIMS: Insulin resistance (IR) and sympathetic over-activation play a critical role in diabetic cardiomyopathy (DCM). Percutaneous renal sympathetic denervation (RDN) was tested to treat refractory hypertension. However, the benefits of RDN for DCM and IR still remain unknown. The present study aimed to investigate the effect and associated mechanisms of bilateral surgical RDN (bsRDN) on cardiac function and glucose metabolism in animals with diabetes. METHODS: Thirty-two male New Zealand white rabbits were randomly assigned to Chow (n=8, normal diet) and TEST (n=24, high-fructose fat diet [HFD]) groups. At 48 weeks after HFD feeding, animals in the TEST group were randomized to the Sham, HFD, and RDN subgroups and were fed a HFD for an additional 8 weeks. Repeated measurements of cardiac function, IR, apoptosis/autophagy, and histopathological assessment were performed at 48 and 56 weeks. RESULTS: HFD feeding for 56 weeks induced IR and diastolic cardiac dysfunction with hypertrophy in septum but well preserved eject fraction in the animals. Impaired IR further deteriorated over the time in the RDN group, featured by a more profound reduction in GLUT4 mRNA and its translocation to the plasma membrane. Successful denervation was associated with improvement of cardiac function via preventing myocardial fibrosis and over-expression of procollagen III, mammalian target of rapamycin, and cardiac apoptosis. Cardiac autophagy, assessed by either electron microscopy or Western blot, was enhanced by bsRDN. CONCLUSIONS: Renal sympathetic denervation led to a significant improvement of HFD-induced cardiac dysfunction by shifting the cardiac apoptosis to autophagy, but worsening IR. Further study is required to identify the clinical benefits of RDN.
Authors: Óscar Julián Arias-Mutis; Patricia Genovés; Conrado J Calvo; Ana Díaz; Germán Parra; Luis Such-Miquel; Luis Such; Antonio Alberola; Francisco Javier Chorro; Manuel Zarzoso Journal: J Vis Exp Date: 2018-04-20 Impact factor: 1.355