Abstract | OBJECTIVES: Extracellular matrix (ECM) remodelling is a critical aspect of cardiac remodelling following myocardial infarction. Tissue inhibitors of metalloproteinases (TIMPs) are physiological inhibitors of matrix metalloproteinases ( MMPs) that degrade the ECM proteins. TIMP-3 is highly expressed in the heart and is markedly downregulated in patients with ischaemic cardiomyopathy. Cell-based gene therapy can enhance the effects of cell transplantation by temporally and spatially regulating the release of the gene product. The purpose of this study was to investigate the role of TIMP-3 gene-transfected vascular smooth muscle cells (VSMCs) in modifying heart structure and function in rats when transplanted 3days after myocardial infarction (MI). METHODS: RESULTS: CONCLUSIONS:
TIMP-3 gene transfection was associated with attenuated left ventricular dilation and recovery of systolic function after MI compared with the control. TIMP-3 transfection enhanced the effects of transplanted VSMCs in rats by inhibiting matrix degradation and inflammatory cytokine expression, leading to improved myocardial remodelling.
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Authors | Zhi-Bo Jia, Hai Tian, Kai Kang, Hong-Zhi Miao, Kai-Yu Liu, Shu-Lin Jiang, Li-Ping Wang |
Journal | Transplant immunology
(Transpl Immunol)
Vol. 30
Issue 4
Pg. 149-58
(May 2014)
ISSN: 1878-5492 [Electronic] Netherlands |
PMID | 24727088
(Publication Type: Journal Article)
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Copyright | Copyright © 2014 Elsevier B.V. All rights reserved. |
Chemical References |
- Tissue Inhibitor of Metalloproteinase-3
- Tumor Necrosis Factor-alpha
- Matrix Metalloproteinase 2
- Matrix Metalloproteinase 9
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Topics |
- Animals
- Cell- and Tissue-Based Therapy
- Echocardiography
- Extracellular Matrix
(physiology)
- Female
- Heart
(physiology)
- Matrix Metalloproteinase 2
(metabolism)
- Matrix Metalloproteinase 9
(metabolism)
- Muscle, Smooth, Vascular
(cytology, metabolism, transplantation)
- Myocardial Infarction
(therapy)
- Myocardium
(pathology)
- Rats
- Rats, Wistar
- Tissue Inhibitor of Metalloproteinase-3
(biosynthesis, genetics)
- Transfection
- Tumor Necrosis Factor-alpha
(metabolism)
- Ventricular Function, Left
(physiology)
- Ventricular Remodeling
(physiology)
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