Chen Han, Wang Rui, Li Quan, Yin Jiasheng, Ge Zhenyi, Xu Fei, Zang Tongtong, Pei Zhiqiang, Li Chaofu, Shen Li, Ge Junbo
Department of Cardiology, Zhongshan Hospital, Fudan University, Research Unit of Cardiovascular Techniques and Devices, Chinese Academy of Medical Sciences, Shanghai, China.
National Clinical Research Center for Interventional Medicine, Shanghai, China.
Front Cardiovasc Med. 2021 Oct 1;8:746934. doi: 10.3389/fcvm.2021.746934. eCollection 2021.
Previous studies have demonstrated the protective effects of renal denervation (RDN) in pre-existing heart failure, but the effects of immediate RDN after acute myocardial infarction (AMI) on subsequent cardiac remodeling have not been reported. This study aimed to investigate the cardioprotective effects of immediate RDN after AMI and its underlying mechanism. AMI was induced by intracoronary gelatin sponge embolization in 14 Shanghai white pigs that were randomized to undergo either renal angiography (AMI+sham group) or RDN (AMI+RDN group) after 1 h of hemodynamic monitoring. Cardiac function of the two groups was measured at baseline, 1 h post-AMI and at the 1 month follow-up (1M-FU) by transthoracic echocardiography (TTE). Plasma NT-proBNP, soluble ST2 (sST2), norepinephrine (NE), and renin-angiotensin-aldosterone system activity were detected simultaneously. The renal cortex was harvested for NE measurement after the 1M-FU, and the renal arteries were stained with tyrosine hydroxylase for the evaluation of sympathetic activity. Heart tissues in the non-ischemic areas were collected to assess histological and molecular left ventricular (LV) remodeling by pathological staining, RT-PCR, and western blotting. There was no difference in the hemodynamic stability or cardiac function between the two groups at baseline and 1 h post-AMI. Six pigs from each of the two groups completed the 1M-FU. TTE analysis revealed the improved cardiac function of immediate RDN in the AMI+RDN group and circulating NT-proBNP levels were lower than those in the AMI+sham group. Further analysis showed significantly less interstitial fibrosis in the remote non-ischemic myocardium after immediate RDN, together with decreased cardiomyocyte hypertrophy and inflammatory cell infiltration. sST2 levels in circulating and myocardial tissues of animals in the AMI+RDN group were significantly higher than those in the AMI+sham group, accompanied by corresponding alterations in IL-33/ST2 and downstream signaling. Immediate RDN can improve cardiac function and myocardial remodeling after AMI via modulation of IL-33/ST2 and downstream signaling.
既往研究已证实肾去神经支配（RDN）对已存在的心力衰竭具有保护作用，但急性心肌梗死（AMI）后即刻进行RDN对后续心脏重塑的影响尚未见报道。本研究旨在探讨AMI后即刻RDN的心脏保护作用及其潜在机制。对14只上海小型猪进行冠状动脉内明胶海绵栓塞诱导AMI，在血流动力学监测1小时后，将其随机分为接受肾血管造影（AMI+假手术组）或RDN（AMI+RDN组）。通过经胸超声心动图（TTE）在基线、AMI后1小时和1个月随访（1M-FU）时测量两组的心脏功能。同时检测血浆N末端B型利钠肽原（NT-proBNP）、可溶性ST2（sST2）、去甲肾上腺素（NE）和肾素-血管紧张素-醛固酮系统活性。1M-FU后采集肾皮质进行NE测量，并用酪氨酸羟化酶对肾动脉进行染色以评估交感神经活性。收集非缺血区域的心脏组织，通过病理染色、逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法评估组织学和分子水平的左心室（LV）重塑。两组在基线和AMI后1小时的血流动力学稳定性或心脏功能无差异。两组各有6只猪完成了1M-FU。TTE分析显示，AMI+RDN组即刻RDN改善了心脏功能，且循环NT-proBNP水平低于AMI+假手术组。进一步分析表明，即刻RDN后远隔非缺血心肌的间质纤维化明显减少，同时心肌细胞肥大和炎性细胞浸润减少。AMI+RDN组动物循环和心肌组织中的sST2水平显著高于AMI+假手术组，同时IL-33/ST2及下游信号发生相应改变。即刻RDN可通过调节IL-33/ST2及下游信号改善AMI后的心脏功能和心肌重塑。
