Elastin Stabilizes an Infarct and Preserves Ventricular Function
Autor: | Richard D. Weisel, Chris Kiani, Ren-Ke Li, Terrence M. Yau, Tomohiro Mizuno |
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Rok vydání: | 2005 |
Předmět: |
Male
Cardiac function curve medicine.medical_specialty Recombinant Fusion Proteins Drug Evaluation Preclinical Myocardial Infarction Transfection Ventricular Function Left Cicatrix Random Allocation Physiology (medical) Internal medicine medicine Animals Single-Blind Method Myocardial infarction Ventricular remodeling Cells Cultured Ultrasonography Heart Failure Ventricular Remodeling biology business.industry Myocardium Endothelial Cells Genetic Therapy medicine.disease Elastin Extracellular Matrix Rats Transplantation medicine.anatomical_structure Rats Inbred Lew Heart failure cardiovascular system biology.protein Cardiology Myocardial infarction complications Hypertrophy Left Ventricular Cardiology and Cardiovascular Medicine business Artery |
Zdroj: | Circulation. 112 |
ISSN: | 1524-4539 0009-7322 |
Popis: | Background— After a myocardial infarction, the injured region becomes fibrotic and the myocardial scar may expand if the ventricular wall lacks elasticity. Cardiac dilatation may precipitate the vicious cycle of progressive heart failure. The present study evaluated the functional benefits of increasing elastin within a myocardial scar using cell based gene therapy. Methods and Results— A myocardial infarction was generated by ligation of the left anterior descending artery in rats. Six days later, 2×10 6 syngeneic rat endothelial cells transfected with the rat elastin gene (elastin group, n=14) or an empty plasmid (control group, n=14) were transplanted into the infarct scar. Cardiac function, left ventricular (LV) volume, and infarct size were monitored over 3 months by echocardiography, Langendorff measurements, and planimetry. Elastin deposition was evaluated in the cells and in the infarct region by Western blot assay and by histological examination. Recombinant elastin was found in the scar in the elastin group but not the control group during the 3 months after cell transplantation. Histological assessment demonstrated organized elastic fibers within the infarct region. LV volume and infarct size were significantly smaller ( P P Conclusions— Expressing recombinant elastin within the myocardial scar reduced scar expansion and prevented LV enlargement after a myocardial infarction. Altering matrix remodeling after an infarct preserved the LV function for at least 3 months. |
Databáze: | OpenAIRE |
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