Hepatocyte growth factor (HGF) alleviates acute and chronic inflammation in experimental inflammatory bowel disease, glomerulonephritis, and airway inflammation. Here, researchers evaluated the anti-inflammatory role of HGF in postischemic heart failure. The left anterior descending coronary artery of rats was ligated, and adenovirus containing human HGF (Ad-HGF) or control GFP adenovirus (Ad-GFP) was injected into the myocardium. Four weeks after injection, left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) were significantly increased in Ad-HGF-treated animals compared with the Ad-GFP group. HGF gene therapy improved ventricular geometry, with a significant decrease in left ventricular end-diastolic diameter (LVEDD) and myocardial collagen deposition. After 4 weeks of Ad-HGF treatment, mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β were significantly reduced in the non-infarcted area. Four weeks after infarction, changes in TNF-α, IL-6, and IL-1β levels in the non-infarcted area were positively correlated with LVEDD. Treatment of acute myocardial infarction (AMI) with Ad-HGF in the early stage of myocardial infarction can reduce the levels of proinflammatory cytokines and protect cardiac function. These results suggest that Ad-HGF gene therapy alleviated ventricular remodeling after infarction by reducing inflammation.
Myocardial infarction rats were treated with Ad-GFP and Ad-HGF for 4 weeks. Hearts in the GFP group (Figure 1A) exhibited significant LV dilatation compared to the sham group (Figure 1C), and HGF treatment (Figure 1B) reduced the LV cavity. Histological analysis showed that the infarct area was significantly increased and the thickness of the left ventricular free wall was significantly reduced in the GFP group. HGF significantly reduced the infarct area and increased the wall thickness (Figures 1D and 1E). The histological differences between myocardial infarction rats treated with Ad-HGF and Ad-GFP were further investigated. Histological changes included myocardial fiber fragmentation and a large number of inflammatory cell infiltration (Figures 1F, 1G, and 1H). The number of lymphocytes in the infarct area of the GFP group was significantly increased compared with the sham group. Ad-HGF treatment significantly protected myocardial cells and reduced inflammatory cell infiltration (Figure 1I).
Figure 1. Cardiac morphology and hematoxylin and eosin staining 4 weeks after treatment. (Rong S, et al., 2018)