Expression levels of matrix metalloproteinases and tissue inhibitor of metalloproteinase in rats with myocardial infarction-caused chronic heart failure following bone marrow mesenchymal stem cell transplantation

Yutao GUO; Xiaoying LI; Di WU; Kequn YAO; Ping CHEN; Kangtao MA; Chunyan ZHOU

ABSTRACT

BACKGROUND:

The content of type Ⅰ and Ⅲ collagen and the ratio of both are crucial factors to promote heart geometric morphology change,and ventricular systolic and diastolic myocardial performance.Matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 1 (TIMP1) are primary regulatory substances of collagen metabolism.After myocardial infarction,chronic heart failure rats were subjected to bone marrow meseuchymal stem cell transplantation.What changes in MMP-2 and TIMPI would occur?

OBJECTIVE:

To observe the content of type Ⅰ and Ⅲcollagen and the ratio between both,as well as expression levels of MMP-2 and TIMP1 in the left ventricular tissue of rats with myocardial infarction-caused chronic heart failure following bone marrow mesenchymal stem cell (MSC) transplantation.

DESIGN:

A randomized controlled experiment.

SETTING:

Department of Senile Angiocardiopathy,General Hospital of Chinese PLA & Department of Biochemistry,Peking University Health Science Center.MATERIALS This study was performed at the laboratory of Department of Biochemistry,Peking University Health Science Center between July 2004 and December 2005.Male Sprage Dawley rats of clean grade,aged 4 weeks old,were provided by the Laboratory Animal Center,Beijing Medical University and used for preparation of MSCs.Fourteen female rats,weighing 200-250g,were developed into models of heart failure-caused by myocardial infarction.

METHODS:

MSCs were isolated and,purified by gradient centrifugation and adherent cells were allowed to proliferate.Female rats underwent coronary artery ligation to induce chronic ischemic heart failure.Four weeks later,the rats were randomly divided into 2 groups (1) experimental group (n=7),rats received transplantation of MSCs harvested from male rats [5×106 in 50 μL phosphate buffered saline(PBS)]by injection into the ischemic myocardium; (2) control group (n=7),rats received the same volume of PBS.MAIN OUTCOME

MEASURES:

Twenty-one days after therapy,(1) left ventricular fusion was tested by hematoxylin-eosinstaining and Masson staining; (2) Expression of MMP-2 and 1TMPI as well as contents of type I and llI collagen was analyzed by immunohistochemistry; (3) MMP-2 and TIMP1 expression levels were examined by Western blot.

RESULTS:

Fourteen rats were included in the final analysis.Type Ⅰ collagen expression in the scar area was much higher in theexperimental group than in the control group,while type Ⅲ collagen expression was much lower in the experimental group.MMP-2 expression was reduced and TIMPI expression was increased in the experimental group compared with the control group.Together,ventricular wall was thickened,ventricular chamber was reduced,and heart function was strengthened in the experimental group compared with the control group.

CONCLUSION:

MSC transplantation alleviated left ventricular remodeling in chronic ischemie heart failure,which results from dynamic regulation of MMP-2/TIMP1.