A Research On The Effects Of MMP-2 And TIMP-2 Expression On Atrial Structural Remodeling In Patients With Atrial Fibrillation Caused By Rheumatic Heart Disease

Objective: (1) To explore the matrix metalloproteinase-2 (MMP-2) and tissue inhibitor-2 of metalloproteinase (TIMP-2) mRNA and protein expression in patients with atrial fibrillation caused by rheumatic heart disease and to evaluate the influence of MMP-2 and TIMP-2 expression on the progress of atrial structural remodeling.(2) To explore the correlationship between the chang of MMP-2 /TIMP-2 expression and the initiation or maintenance of atrial fibrillation caused by rheumatic heart disease.Methods: (1) 42 patients with chronic atrial fibrillation(AF) caused by mitral valve straitness of rheumatic heart disease were as experimental group, and 18 patients with sinus rhythm were as control group. Left atrial appendage (LAA) tissue samples were obtained from these patients during mitral valve replacement operation.(2) Before operation, all of the patients above underwent transthoracic echocardiograph, and related clinical date were collected. The content of collagen fibers in left atrial appendage were observed by Masson trichrome stain. MMP-2 and TIMP-2 protein expressions were detected by immunohistochemistry and their mRNA expressions were determined by reverse transcription polymerase chain reaction(RT-PCR).Results : (1) Compare with control group, the content of collagen fibers in left atrial appendage increased significantly in patients with AF(p< 0.01). The content of collagen fibers in left atrial appendage was significantly correlated with LAD (r=0.788, P<0.001) ,CTR (r=0.664, P<0.05) and the aera of mitral valve(r=-0.886, P<0.05).(2) Compare with control group, the expressions of MMP-2 mRNA(P<0.05)and protein (p<0.05) in the LAA tissue of the AF group is up regulated significantly;the expressions of TIMP-2 mRNA(P <0.05)and protein (p<0.05) in the LAA tissue of the AF group is down regulated significantly.(3) The expressions of MMP-2 mRNA in LAA tissue was significantly correlated with TIMP-2 mRNA (r = -0.766, P<0.001) . The MMP-2 mRNA was significantly correlated with MMP-2 protein (r=0.871, P<0.001) . The TIMP-2 mRNA was significantly correlated with TIMP-2 protein(r=0.799, P<0.001). The expressions of MMP-2 mRNA and protein was significantly correlated with LAD (P<0.05) ,CTR(P<0.05), the aera of mitral valve(P<0.05) and the content of collagen fibers in left atrial appendage (P<0.01) . The expressions of TIMP-2 mRNA and protein was significantly correlated LAD (P<0.05) ,CTR(P <0.05) ,the aera of mitral valve(P<0.05) and the content of collagen fibers in left atrial appendage (r_p= -0.830, P<0.001) .Conclusion: (1) The selective downregulation of TIMP-2 and upregulation of MMP-2 gene expression in atrium, especially the unbalance change of the MMP-2 and TIMP-2 gene expression, could be one of the important molecular mechanisms of atrial structural remodeling in patients with atrial fibrillation caused by rheumatic heart disease.(2) The chang of the gene expression of MMP-2/TIMP-2 could be an important molecular mechanisms of the initiation and maintenance of AF.(3) To control the related MMPs/TIMPs expression and to adjust the balances of MMPs/ TIMPs, could be able to prevent and deter atria from expanding and fibrosis, and then taking prevention and delaying the initiation and maintenance of AF.