2007•Shandong yiyaoRequires access
Effect of MMP-2/TIMP-2 in extracellular matrix remodeling in the hearts of STZ-induced diabetic rats
Minghua Liu
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Abstract
[Objective] To observe the changes of MMP-2/TIMP-2 in the hearts of streptozotocin-induced diabetic rats and gain insight into their roles in ECM remodeling on an experimental animal model of diabetic cardiomyopathy.[Methods] 16 male Wistar rats were randomly divided into two groups: normal control group and diabetic rats group.Diabetes mellitus was induced by intraperitoneal injection of streptozotocin.At the end of 4 weeks,serum MMP-2 and TIMP-2 levels were examined by enzyme linked immunosorbent assay(ELISA).Cardiac MMP-2 activity was detected by gel zymography.TIMP-2 protein expression was analyzed by immunohistochemistry.MMP-2 and TIMP2 gene expressions were measured by reverse transcription polymerase chain reaction(RT-PCR).Cardiac collagen contents were analyzed by Van Gieson(VG) staining and the results were quantified by densitometry.[Results] Diabetes mellitus was associated with a decreased body weight and heart weight but an increased HW/BW.In the diabetic group,serum MMP-2 levels had a tendency to increase but not significantly,while serum TIMP-2 significantly increased.Both the activity and expression of MMP-2 decreased in the hearts of diabetic rats.TIMP-2 gene expression in myocardium increased significantly.VG staining showed a marked deposition of collagen in diabetic group.Multivariate analysis revealed that total collagen contents correlated negatively with the activity and gene expression of MMP-2 in the myocardium,and correlated positively with TIMP-1 mRNA expression.[Conclusions] The decrease in MMP-2 activity and expression and increase in TIMP-2 expression in the myocardium of diabetic rats may lead to impairment of collagen degradation and contribute to the matrix deposition in diabetic myocardiopathy.The correlation between the serum level and cardiac expression of TIMP-2 in diabetic rats suggests that serum TIMP-2 level may be a viable marker for early diagnosis of diabetic myocardiopathy.