HO-1 modified mesenchymal stem cells modulate MMPs/TIMPs system and adverse remodeling in infarcted myocardium |
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Authors: | Tao Shu Bin Zeng Xiaofeng Ren |
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Institution: | a Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China b Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, PR China c College of Veterinary Medicine, Northeast Agricultural University, Harbin, Hei Longjiang, PR China d Department of E.N.T. Sha Yang people's Hospital, Sha Yang, Hu Bei 448200, PR China |
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Abstract: | The present study was to determine the effects of the heme oxygenase-1 (HO-1) modified mesenchymal stem cells (MSCs) transplantation into acute MI hearts on normalizing the ratio of MMPs/TIMPs and remodeling in infarcted myocardium. HO-1 was transfected into cultured MSCs using an adenoviral vector. 1 × 106 Ad-HO-1-transfected MSCs (HO-1-MSCs) or Ad-Null-transfected MSCs (Null-MSCs) or PBS was respectively injected into rat hearts 1 h intramyocardially after myocardial infarction. The cardiac performance was significantly improved and left ventricular dilatation was significantly attenuated in HO-1-MSCs transplanted hearts. Moreover, a significant increase in microvessel density was observed in HO-1-MSCs transplanted hearts. TIMP2,3 expression in HO-1-MSCs transplanted hearts was significantly increased, and MMP2,9 expression in HO-1-MSCs transplanted hearts was significantly lower than Null-MSCs transplanted and PBS-treated hearts. TIMP1 expression did not vary significantly. Null-MSCs transplantation did not decrease the expression of MMP2,9 significantly compared with PBS-treated hearts. The ratio of TIMP2 to MMP2, and TIMP3 to MMP9 in cell-grafted hearts was increased significantly. HO-1-MSCs transplantation normalize the ratio of MMPs/TIMPs, contributing to the reversion of myocardial extracellular remodeling. |
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Keywords: | Myocardial infarction Mesenchymal stem cells Heme oxygenase-1 Extracellular matrix Remodeling |
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