Matrix metalloproteinase inhibition attenuates early left ventricular enlargement after experimental myocardial infarction in mice
| Autor: | Peter G. Mitchell, Luis H. Arroyo, Kim Francis Mcclure, Peter Libby, Luis Eduardo Paim Rohde, Galina H. Sukhova, Arturo Lopez-Anaya, Richard T. Lee, Anique Ducharme, Masanori Aikawa |
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| Rok vydání: | 1999 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Myocardial Infarction Infarction Mice Inbred Strains Placebo Muscle hypertrophy Mice Physiology (medical) Internal medicine medicine Halogenated Diphenyl Ethers Animals Protease Inhibitors Myocardial infarction Ventricular remodeling business.industry Myocardium Phenyl Ethers Metalloendopeptidases Papillary Muscles medicine.disease Surgery medicine.anatomical_structure Echocardiography Cardiology Myocardial infarction complications Hypertrophy Left Ventricular Cardiology and Cardiovascular Medicine Ligation business Artery |
| Zdroj: | Circulation. 99(23) |
| ISSN: | 1524-4539 |
| Popis: | Background —Extracellular matrix synthesis and degradation contribute to the morphological changes that occur after myocardial infarction (MI). Methods and Results —We tested the hypothesis that inhibition of matrix metalloproteinases (MMPs) attenuates left ventricular remodeling in experimental MI. Seventy-one male FVB mice that survived ligation of the left anterior coronary artery were randomized to a broad-spectrum MMP inhibitor (CP-471,474) or placebo by gavage. Echocardiographic studies were performed before randomization (within 24 hours of surgery) and 4 days later and included short-axis imaging at the midpapillary and apical levels. Infarction as defined by wall motion abnormality was achieved in 79% of the procedures (n=56), and mortality rate during the 4-day protocol was 23% (9 of 36 on treatment vs 7 of 35 on placebo; P =NS). Baseline end-diastolic and end-systolic dimensions and areas were similar ( P =NS) between treated and placebo groups. At follow-up, infarcted mice allocated to MMP inhibitor had significantly smaller increases in end-systolic and end-diastolic dimensions and areas at both midpapillary and apical levels compared with infarcted mice allocated to placebo (all P P P Conclusions —–Administration of an MMP inhibitor attenuates early left ventricular dilation after experimental MI in mice. Further studies in genetically altered mice and other models will improve understanding of the role of MMPs in left ventricular remodeling. |
| Databáze: | OpenAIRE |
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