PMID- 26556551 OWN - NLM STAT- MEDLINE DCOM- 20161025 LR - 20220309 IS - 1469-445X (Electronic) IS - 0958-0670 (Linking) VI - 101 IP - 2 DP - 2016 Feb TI - Possible mechanism by which renal sympathetic denervation improves left ventricular remodelling after myocardial infarction. PG - 260-71 LID - 10.1113/EP085302 [doi] AB - What is the central question of this study? The enzyme system that is responsible for extracellular matrix (ECM) turnover is the matrix metalloproteinases (MMPs), which can be blocked by the tissue inhibitors of MMPs (TIMPs). Whether renal sympathetic denervation (RSD) is able to ameliorate post-myocardial infarction left ventricular remodelling through attenuation of ECM via regulation of MMP activity and/or the MMP-TIMP complex remains unknown. What is the main finding and its importance? Renal sympathetic denervation has therapeutic effects on post-myocardial infarction left ventricular remodelling, probably by attenuating the ECM through regulation of the MMP9-TIMP1 complex in the transforming growth factor-beta1 (a profibrotic cytokine that accelerates ECM remodelling after ischaemia) signalling pathway. Whether renal sympathetic denervation (RSD) is able to ameliorate post-myocardial infarction (post-MI) left ventricular (LV) remodelling by attenuation of the extracellular matrix via regulation of matrix metalloproteinase (MMP) activity and/or the MMP-tissue inhibitor of matrix metalloproteinase (TIMP) complex remains unknown. Sixty-five Sprague-Dawley rats were randomly divided into the following four groups: normal (N, n = 15), RSD (RSD, n = 15), myocardial infarction (MI, n = 15) and RSD 3 days after MI (MI3d+RSD, n = 20). The bilateral renal nerves were surgically denervated 3 days after MI had been induced by coronary artery ligation. Left ventricular function was assessed using echocardiography and a Millar catheter at 6 weeks post-MI. Plasma noradrenaline, angiotensin II and aldosterone, collagen volume fraction, transforming growth factor-beta1 (TGF-beta1), MMP2, MMP9 and TIMP1 in heart tissue were measured 6 weeks after MI. In rats with MI3d+RSD compared with MI rats, RSD improved systolic and diastolic function, resulting in an improvement in ejection fraction (P < 0.05), fractional shortening (P < 0.05) and LV internal dimension in systole (P < 0.05) and diastole (P < 0.05). Additionally, RSD treatment decreased left ventricular end-diastolic pressure (P < 0.05) and increased LV systolic pressure (P < 0.05) and maximal and minimal rate of LV pressure (both P < 0.05). Meanwhile, RSD reduced collagen content (P < 0.01). TIMP1 was upregulated (P < 0.05), whereas MMP2, MMP9 and TGF-beta1 were downregulated in the LV of RSD-treated animals (P < 0.05). Renal sympathetic denervation has therapeutic effects on post-MI LV remodelling, probably owing to effects on the extracellular matrix by regulation of the MMP9-TIMP1 balance in the TGF-beta1 signalling pathway. Renal sympathetic denervation may be considered as a non-pharmacological approach for the improvement of post-MI cardiac dysfunction. CI - (c) 2015 The Authors. Experimental Physiology (c) 2015 The Physiological Society. FAU - Zheng, Xiao-Xin AU - Zheng XX AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China. AD - Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China. FAU - Li, Xiao-Yan AU - Li XY AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China. AD - Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China. FAU - Lyu, Yong-Nan AU - Lyu YN AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China. AD - Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China. FAU - He, Yi-Yu AU - He YY AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China. AD - Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China. FAU - Wan, Wei-Guo AU - Wan WG AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China. AD - Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China. FAU - Zhu, Hong-Ling AU - Zhu HL AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China. AD - Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China. FAU - Jiang, Xue-Jun AU - Jiang XJ AD - Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China. AD - Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151216 PL - England TA - Exp Physiol JT - Experimental physiology JID - 9002940 RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - 0 (Transforming Growth Factor beta1) RN - 9007-34-5 (Collagen) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Animals MH - Blood Pressure/physiology MH - Collagen/metabolism MH - Diastole/physiology MH - Heart Ventricles/metabolism/*physiopathology MH - Kidney/*innervation MH - Male MH - Matrix Metalloproteinase 2/metabolism MH - Matrix Metalloproteinase 9/metabolism MH - Myocardial Infarction/metabolism/*physiopathology MH - Rats MH - Rats, Sprague-Dawley MH - Signal Transduction/physiology MH - Sympathectomy/methods MH - Systole/physiology MH - Tissue Inhibitor of Metalloproteinase-1/metabolism MH - Transforming Growth Factor beta1/metabolism MH - Ventricular Dysfunction, Left/metabolism/physiopathology MH - Ventricular Function, Left/*physiology MH - Ventricular Remodeling/*physiology EDAT- 2015/11/12 06:00 MHDA- 2016/10/26 06:00 CRDT- 2015/11/12 06:00 PHST- 2015/04/25 00:00 [received] PHST- 2015/11/05 00:00 [accepted] PHST- 2015/11/12 06:00 [entrez] PHST- 2015/11/12 06:00 [pubmed] PHST- 2016/10/26 06:00 [medline] AID - 10.1113/EP085302 [doi] PST - ppublish SO - Exp Physiol. 2016 Feb;101(2):260-71. doi: 10.1113/EP085302. Epub 2015 Dec 16.