Changes of angiogenesis with aging in kidneys of human TIMP-1 transgenic mice and its significance

Objective To explore the effect of tissue inhibitor of metalloproteinase(TIMP)-1 on renal angiogenesis with aging.Methods Changes of microvascular density(MVD) in kidneys in wild type mice and transgenic mice at the age of 3,12,24 months were observed by periodic acid-sliver methenamine(PASM) staining of paraffin sections.The protein expressions of TIMP-1,TIMP-2,matrix metalloproteinase(MMP)-9,MMP-2,vascular endothelial growth factor(VEGF),collagen Ⅲ and Ⅳ were detected by Western blotting.The activities of gelatinases and TIMP-1 were examined by gelatin zymography and reverse zymography respectively.Results At the age of 24 months,MVD was lower,expressions of collagen Ⅲ and Ⅳ protein and TIMP-1 were higher,the expressions of MMP-2,-9 and VEGF were higher,the activities of gelatinases and TIMP-1 were downregulated and upregulated respectively(all P 0.05).Conclusions TIMP-1 could promote age-related renal insenecence through affecting angiogenesis.