Expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases in the model of left ventricular mechanical unloading

Objective To study the expression of matrix metalloproteinases (MMPs) and their tissue inhibitor (TIMPs) in the model of left ventricular mechanical unloading and to explore the molecular mechanism of cardiac reverse remodeling after left ventricular unloading.Methods Lewis rats underwent left anterior descending artery ligation.Four weeks later,14 rats with heart failure were randomly divided into heart failure group (HF,n=7) and heart transplantation group (HT,n=7).Heart and right lung of heart failure donors from HT group were transplanted into normal recipient rats,with ascending aorta of doners anastomosed with descending aorta of recipients.Another 7 normal rats were enrolled as controls.Four weeks after ligation,heart ultrasonography was performed to detect the ventricle diameter and myocardial infarction (MI) field of the three groups.Two weeks later after transplantation,heart mass and left ventricular mass were weighted,myocyte diameter and myocardial fibrosis were evaluated under microscope.Expression of MMP-1,MMP-9,TIMP-1 and proportion of MMP-1/TIMP-1 mRNA were examined by real-time polymerase chain reaction (PCR).Results Four weeks later after ligation,left ventricular end- diastolic diameter (LVEDD) increased but left ventricular fractional shortening (LVFS) decreased in both HF and HT groups when comparing with the normal controls.No statistical significance of LVEDD,LVFS,MI field and heart failure severity was observed between HF and HT groups.Heart mass,left ventricle mass and myocyte diameter were higher in HF group than those of HT group and controls,and those parameters in HT group were almost normal.The severity of myocardial fibrosis was as follows: HT group ＞ HF group ＞ controls [ (7.90±2.32) ％ vs (4.20± 1.84) ％ vs ( 1.54±0.31 ) ％,all P＜0.05 ].The levels of MMP- 1 and MMP-9 mRNA were significantly higher in HF group and HT group than those in normal group (1.89±0.23,1.32±0.16 vs0.41±0.01; 2.03±0.15,1.50±0.13 vs 0.46±0.01,all P＜0.05),and these parameters of HF group and HT group had no statistical significance.The level of TIMP- 1 mRNA was lower in HF group than that in normal group and HT group (0.72±0.18 vs 1.21 ±0.02,1.68±0.21,all P＜0.05),and the difference was not significant between normal group and HT group.The MMP-1 mRNA/TIMP-1mRNA was higher in HF group as compared to other two groups (2.03±0.15 vs 0.30±0.01,0.81±0.11,all P＜0.05),and the difference was not significant between normal group and HT group.Conclusion After left ventricular unloading,the reverse remodeling of myocardial tissue happens with the changes of MMPs and TIMPs levels in myocytes. Key words: Matrix metalloproteinases ;  Tissue inhibitor of metalloproteinases;  Heart - lung transplantation ;  Heart failure;  Models, animal