Article

Anti-inflammatory activities of hepatocyte growth factor in post-ischemic heart failure

Authors: Shu-ling RONG1, Xiao-lin WANG2, Yi-cheng WANG3, Huan WU4, Xue-dong ZHOU5, Ze-kun WANG5, Yu-chuan WANG1, Cun-shui XUE6, Bao LI1, Dong-lai GAO1
1 Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan 030001, China
2 Department of Pediatrics, The Second Hospital of Shanxi Medical University, Taiyuan 030001, China
3 Department of Cardiology, Heping Hospital, Changzhi Medical College, Changzhi 046000, China
4 Department of Pediatrics, Heping Hospital, Changzhi Medical College, Changzhi 046000, China
5 Department of Conservative Dentistry, West China School of Stomatology and State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China
6 Department of Neurology, The Second Hospital of Shanxi Medical University, Taiyuan 030001, China
Correspondence to: Xiao-lin WANG: czsrsl@sina.com, Bao LI: libaoxys@163.com,
DOI: 10.1038/aps.2018.14
Received: 19 October 2017
Accepted: 28 February 2018
Advance online: 24 May 2018

Abstract

Hepatocyte growth factor (HGF) alleviates acute and chronic inflammation in experimental inflammatory bowel disease, glomerulonephritis, and airway inflammation. However, the anti-inflammatory effects of HGF on myocardial infarction are not defined. The current study assessed the anti-inflammatory effects of HGF in post-ischemic heart failure. The left anterior descending coronary artery was ligated in rats, and adenovirus containing human HGF (Ad-HGF) or control virus (Ad-GFP) was administered intramyocardially. The quantity of proinflammatory cytokines secreted by cardiomyocytes, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β, was evaluated. Cardiac function and LV remodeling were assessed using echocardiography and collagen deposition, respectively. Left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) four weeks after injection were significantly increased in Ad-HGF-treated animals compared to the Ad-GFP group. HGF gene therapy improved ventricular geometry with a significantly decreased left ventricular end-diastolic diameter (LVEDD) and markedly reduced myocardial collagen deposition. Treatment with Ad-HGF significantly decreased the mRNA levels of TNF-α, IL-6, and IL-1β in the non-infarcted region four weeks after injection. Changes of the TNF-α, IL-6, and IL-1β levels in the non-infarcted region positively correlated with the LVEDD 4 weeks after infarction. Treatment of acute myocardial infarction (AMI) with Ad-HGF in the early stage of MI reduced the pro-inflammatory cytokine levels and preserved cardiac function. These findings indicated that Ad-HGF gene therapy alleviated ventricular remodeling after infarction by reducing inflammation.
Keywords: hepatocyte growth factor; gene therapy; ventricular remodeling; inflammatory cytokines; myocardial infarct

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