Tissue inhibitor of metalloproteinases-4 suppresses vascular smooth muscle cell migration and induces cell apoptosis.
In a previous study, we have demonstrated that overexpression of the tissue inhibitors of metalloproteinases-4 (TIMP-4) can inhibit the neointima formation in the rat carotid model. To define the functions of tissue inhibitor of metalloproteinases-4 (TIMP-4) in SMCs, we transduced human TIMP-4 cDNA into rat aortic SMCs by using adenoviral vector. Overexpression of TIMP-4 blocked the conversion of pro-MMP-2 to the active form and inhibited basic fibroblast growth factor-induced migration by 56.7% (p < 0.01). Overexpression of TIMP-4 markedly increased apoptotic cell death without changing their proliferation. Importantly, overexpression of human TIMP-4 in the wall of balloon-injured rat carotid artery also increased SMC apoptosis. The percentages of TUNEL-positive cells of total cells increased significantly in AdTIMP-4 infected group compared with AdGFP infected group. These findings demonstrate that TIMP-4 can inhibit SMCs migration and induce apoptosis in vitro and in vivo, which may generate new targets for prevention and treatment of vascular diseases.
Guo
Yan-Hong
YH
Institute of Cardiovascular Sciences, Peking University, No. 38, Xue Yuan Road, Beijing, PR China.
Gao
Wei
W
Li
Qian
Q
Li
Peng-Fei
PF
Yao
Peng-Ying
PY
Chen
Kuanghueih
K
D000800:Angioplasty, Balloon; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D020212:Carotid Artery Injuries / Q000188:drug therapy*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019714:Tissue Inhibitor of Metalloproteinases / Q000494:pharmacology*; D000097792:Tissue Inhibitor of Metalloproteinase-4
D004791:Enzyme Inhibitors; D008666:Metalloendopeptidases; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4