Overexpression of TIMP-2 mediated by recombinant adenovirus in rat abdominal aorta inhibits extracellular matrix degradation.
To investigate the effects of a tissue inhibitor of the matrix metalloproteinase-2 (TIMP-2) gene on the extracellular matrix of the abdominal aorta, models of rat abdominal aortic aneurysm were utilized and a solution of AdTIMP-2 was perfused into the abdominal aorta. The models of rat abdominal aortic aneurysm were constructed with intraluminal perfusion of the abdominal aorta with porcine pancreatic elastase, and an adenovirus solution carrying the TIMP-2 gene was transferred into the aorta by local perfusion. After 14 days, aortic wall elastin and collagen concentrations were measured with an image analysis system and fixed aortic tissues were examined by light microscopy for inflammation. No abdominal aortic aneurysms developed in TIMP-2 gene-transferred rat models, representing a marked decreased from control rats (p < 0.01). The elastic fibers and collagenous fibers were preserved with greater integrity in the AdTIMP-2 group than in the control group and inflammatory cells were seen in adventitial areas. The TIMP-2 gene mediated by adenovirus can renew the balance of degradation of the extracellular matrix caused by elastase and inhibit the formation of an abdominal aortic aneurysm. This finding provides a new strategy for treatment of abdominal aortic aneurysms.
Zhao
Xin
X
Hepato-Biliary-Pancreatic Surgery Division, the General Hospital of PLA, Beijing, China.
Li
Hailin
H
Dong
Jiahong
J
Kokudo
Norihiro
N
Tang
Wei
W
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D015316:Genetic Therapy; D008297:Male; D008853:Microscopy; D051381:Rats; D017207:Rats, Sprague-Dawley; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D019716:Tissue Inhibitor of Metalloproteinase-2