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The roles of MMP-2/TIMP-2 in extracellular matrix remodelling in the hearts of STZ-induced diabetic rats.

Authors: Li, Q  Sun, SZ  Wang, Y  Tian, YJ  Liu, MH 
Citation: Li Q, etal., Acta Cardiol. 2007 Oct;62(5):485-91.
Pubmed: (View Article at PubMed) PMID:17982970
DOI: Full-text: DOI:10.2143/AC.62.5.2023412

OBJECTIVE: The present study was designed to examine the changes of MMP-2/TIMP-2 in the hearts of streptozotocin-induced diabetic rats and gain insight into their roles in extracellular matrix (ECM) remodelling on an experimental animal model of diabetic cardiomyopathy. METHODS AND RESULTS: Sixteen male Wistar rats were randomly divided into two groups: normal control and diabetic rats. Diabetes mellitus was induced in rats by streptozotocin injection. All rats were fed with standard chow and water ad libitum for 4 weeks. At 4 weeks diabetic rats were associated with a lower body weight (BW) and heart weight (HW) but a higher HW/BW. In the diabetic group, serum MMP-2 level had a tendency to increase but not significantly, while serum TIMP-2 significantly increased. Both the activity and expression of MMP-2 weakened in the hearts of diabetic rats. TIMP-2 gene expression in myocardium enhanced significantly. TIMP-2 protein level in diabetic heart was strengthened slightly but not significantly. VG staining showed a marked deposition of collagen in the diabetic group. Multivariate analysis revealed that total collagen content 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 gene 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 suggested that serum TIMP-2 level may be a viable marker for early diagnosis of diabetic myocardiopathy.


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CRRD Object Information
CRRD ID: 2290406
Created: 2008-03-11
Species: All species
Last Modified: 2008-03-11
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.