Abstract | BACKGROUND: METHODS AND RESULTS: Adenoviral vector expressing ILK (n=25) or empty adeno-null (n=25) was injected into rat peri- infarct myocardium after left anterior descending coronary artery ligation. ILK expression was confirmed by Western blotting and immunofluorescence. Echocardiographic and hemodynamic analyses demonstrated relatively preserved cardiac function in adeno-ILK animals. ILK treatment was associated with reduced infarct scar size, increased scar thinning ratio, and preserved LV diameter, wall thickness, cardiomyocyte size, and myofilament density. Enhanced angiogenesis and reduced fibrosis were observed in the adeno-ILK group, along with reduced apoptosis as demonstrated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling analysis. Moreover, increased cardiomyocyte proliferation was found in adeno-ILK animals, as measured by proliferating cell nuclear antigen, Ki-67, and phosphohistone-H3 staining. At long-term follow-up, most indices of cardiac function and hemodynamics showed no difference between adeno-ILK and control animals by 9 weeks, although LV end-systolic diameter and infarct scar size were reduced in the adeno-ILK group at this time point. Additionally, ILK overexpression was found to exert a rescue effect on remodeling when administered in a delayed fashion 1 week after coronary artery ligation. CONCLUSIONS: ILK gene therapy improves cardiac remodeling and function in rats after myocardial infarction and is associated with increased angiogenesis, reduced apoptosis, and increased cardiomyocyte proliferation. This may represent a new approach to the treatment of postinfarct remodeling and subsequent heart failure.
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Authors | Liang Ding, Li Dong, Xin Chen, Lujie Zhang, Xiaoyu Xu, Albert Ferro, Biao Xu |
Journal | Circulation
(Circulation)
Vol. 120
Issue 9
Pg. 764-73
(Sep 01 2009)
ISSN: 1524-4539 [Electronic] United States |
PMID | 19687354
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers
- integrin-linked kinase
- Protein Serine-Threonine Kinases
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Topics |
- Adenoviridae
(genetics)
- Animals
- Apoptosis
(physiology)
- Biomarkers
- Cell Division
(physiology)
- Disease Models, Animal
- Genetic Therapy
(methods)
- Heart Function Tests
- Male
- Myocardial Infarction
(physiopathology, therapy)
- Myocytes, Cardiac
(cytology, physiology)
- Neovascularization, Physiologic
(physiology)
- Protein Serine-Threonine Kinases
(genetics)
- Rats
- Rats, Sprague-Dawley
- Ventricular Remodeling
(physiology)
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