期刊
DIABETOLOGIA
卷 46, 期 10, 页码 1438-1445出版社
SPRINGER
DOI: 10.1007/s00125-003-1200-y
关键词
fibrosis; TUNEL; endocardial endothelium; MMP; TIMP; hypertension; heart failure
资金
- NHLBI NIH HHS [HL-71010, HL-74185] Funding Source: Medline
- NIGMS NIH HHS [GM-48595] Funding Source: Medline
Aims/hypothesis. Although matrix metalloproteinase-9 (MMP-9) is specifically induced and apoptosis of endothelial cells is evidenced in diabetes mellitus, the mechanism of endocardial endothelial dysfunction in diabetes mellitus is not clear. The increase in MMP-9 activity is associated with endocardial endothelial apoptosis and dysfunction in diabetes mellitus. Methods. Diabetes was created by injecting 65 mg/kg alloxan in tail vein of MMP-9 knockout (-/-) and wild-type (WT, C57BL/J6) mice. At 8 weeks mice were grouped: (i) WT+saline; (ii) WT+alloxan; (iii) MMP+saline; (iv) MMP+alloxan. The MMP-9 genotype was determined by observing single PCR product of different mobility than the PCR product from wild-type in blood from tail vein. Results. MMP-9 activity, measured by zymography, increased in plasma and in the left ventricle of alloxan-induced diabetic wild-type mice. The concentrations of cardiac inhibitor of metalloproteinase, that blocks MMP-9 activity, were decreased in diabetic MMP-9 knockouts as well as in wild-type mice. Diabetes induced apoptosis, detected by TUNEL assays, in wild-type but not in MMP-9 knockouts. Endocardial endothelial function was severely impaired in diabetic wild-type mice compared with normoglycaemic animals, while non-diabetic MMP-9 knockout mice showed partial endocardial endothelial dysfunction which was not further exacerbated by the developments of diabetes. Conclusion/interpretation. The results suggest an association between increased MMP-9 activity and endocardial endothelial apoptosis in diabetic mice, while genetic ablation of MMP-9 correlated with amelioration of endocardial endothelial dysfunction and apoptosis.
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