[In vivo interleukin-10 gene transfer down-regulates myocardial matrix metalloproteinase and myocardial collagen expressions in rats with acute myocardial infarction].
OBJECTIVE
We investigated the in vivo effects of recombinant adenovirus-associated virus type-2 (AAV-2) mediated interleukin-10 (IL-10) gene transfer on the expression of matrix metalloproteinase (MMP)-2, 9, tissue inhibitor of metalloproteinase (TIMP)-1, collagen type I and type III in a rat acute myocardial infarction model.


METHODS
Male Sprague-Dawley (SD) rats were randomly divided into three groups (each n = 6): sham operation group, MI/AAV2 group, and MI/AAV2-IL-10 group (10(10) vg/ml x 0.1 ml injection at peri-infarct regions immediately post MI). Five days later, the expressions of MMP-2 and MMP-9 were measured by RT-PCR, Western blot and zymography. The expression of TIMP-1 was measured by RT-PCR and Western blot. Collagen type I and type III were assessed by RT-PCR and immunohistochemical stain.


RESULTS
The myocardial expressions of MMP-2, MMP-9 and collagen contents in MI/AAV2 group were significantly increased than those in sham operation group. Myocardial expressions of MMP-2, MMP-9 were significantly decreased and the expression of TIMP-1 significantly increased in the MI/AAV2-IL-10 group than those in MI/AAV2 group. Moreover, the expressions of collagen type I, collagen type III and the ratio of I/III collagen in border zones of infarcted myocardium were decreased by 47.6% (P < 0.01), 23.6% (P < 0.05), and 17.9% (P < 0.05) respectively, while the expression of TIMP-1 increased by 73.1%(P < 0.05) in MI/AAV2-IL-10 group compared to MI/AAV2 group.


CONCLUSIONS
In vivo myocardial IL-10 transfer reduced myocardial MMP and collagen expression and increasing the TIMP expression.
Hu
Chun-Yang
CY
Department of Cardiology, Peking University First Hospital, Beijing 100034, China.
Ding
Wen-Hui
WH
Han
Xiao-Ning
XN
Chu
Song-Yun
SY
Hao
Yan-Jie
YJ
Bu
Ding-Fang
DF
D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism*; D015870:Gene Expression; D015316:Genetic Therapy; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014162:Transfection; D020257:Ventricular Remodeling
D019715:Tissue Inhibitor of Metalloproteinase-1; D016753:Interleukin-10; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9