Effects Of MMP-1 And TIMP-1 On Myocardial Extracellular Matrix Remodeling In Hypertrophic Rat Hearts Induced By Aortic Coarctation

BackgroundIn response to a variety of mechanical, hemodynamic, hormonal, and pathologic stimuli, the heart adapts to increased demands for cardiac work by increasing muscle mass through the initiation of a hypertrophic response. Cardiac hypertrophy is observed in various cardiovascular diseases such as hypertension, valvular heart diseases, and hypertrophic cardiomyopathy. Clinical studies have demonstrated that cardiac hypertrophy is not only an adaptational state before heart failure but is an independent risk factor for ischemia, arrhythmia, and sudden death. The accumulation of extracellular matrix (ECM) in the heart plays an important role in the development of cardiac hypertrophy. Myocyte hypertrophy and interstitial fibrosis in left ventricle (LV), referred to as remodeling ,contribute to development of depressed cardiac performance .Accordingly, it is of critical importance to understand the underlying mechanisms of cardiac hypertrophy and to develop therapeutic strategies that will effectively inhibit the development and progression of LV remodeling.Cardiac extracellular matrix (ECM) consists of several groups of extracellular macromolecules. As a major component, cardiac collagen provides alignment to myocardial cells and serves as the skeleton of cardiac collagen network, which maintains the ventricular chambers in normal structural architecture and function. The matrix metalloproteinases (MMPs) are a family of structurally related endopeptidases that have the ability to degrade all components of the extracellular matrix, so they are the major physiological regulators of the extracellular matrix.ObjectiveThe study was to investigate the role of collagen, metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in cardiac hypertrophy and extracellular matrix remodeling and effect of operation on cardiac hypertrophy due to pressure overload.MethodsThirty healthy Wistar rats weighing 160g～200g were randomly divided into three groups: control group(n=10), experiment group(n=10) and treatment group(n=10). Experiment group and treatment group rats were achieved by partially banding abdominal aortic artery. Cardiac hypertrophy due to pressure overload was produced by partially banding abdominal aortic artery. After modeling myocardial hypertrophy of rats the abdominal aortic band was removed. 8 weeks later, the changes of hemodynamics were measured before the rats were killed. And then the pathobiological changes of the hearts, the collagen expression and the index of cardiac hypertrophy were measured. Eventually the expressions of MMP-1 mRNA and TIMP-1 mRNA were tested by Real-time PCR.ResultsAbdominal aortic banding induced hypertrophy and extracellular matrix remodeling predominantly occurred on the left ventricular. The myocardial content of collagen and expressions of MMP-1 mRNA, TIMP-1 mRNA of experiment group and treatment group rats were elevated (PO.05). After removing abdominal aortic band the index of cardiac hypertrophy and BP of treatment group rats were degraded (P<0.05), the total collagen and the expression of MMP-1 were decreased (P<0.05).Conclusions1. The content of collagen and expressions of MMP-1 mRNA, TIMP-1 mRNA in hypertrophic hat hearts induced by partially banding abdominal aortic artery were elevated obviously.2. Removing abdominal aortic band can prevent the myocardial hypertrophy and extracellular matrix remodeling and the synthesis of collagen and expressions of the MMP-1, TIMP-1 were decreased.3. MMP-1 and TIMP-1 participated in the process of extracellular matrix remodeling in hypertrophic hat hearts.