Establishment of a Novel Murine Model of Ischemic Cardiomyopathy with Multiple Diffuse Coronary Lesions |
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| Authors: | Hajime Nakaoka Yumiko Nakagawa-Toyama Makoto Nishida Takeshi Okada Ryota Kawase Taiji Yamashita Miyako Yuasa-Kawase Kazuhiro Nakatani Daisaku Masuda Tohru Ohama Takashi Sonobe Mikiyasu Shirai Issei Komuro Shizuya Yamashita |
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| Institution: | 1. Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.; 2. Health Care Center, Osaka University, Toyonaka, Osaka, Japan.; 3. Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan.; 4. Department of Community Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.; Albert Einstein College of Medicine, United States of America, |
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| Abstract: | ObjectivesAtherosclerotic lesions of the coronary arteries are the pathological basis for myocardial infarction and ischemic cardiomyopathy. Progression of heart failure after myocardial infarction is associated with cardiac remodeling, which has been studied by means of coronary ligation in mice. However, this ligation model requires excellent techniques. Recently, a new murine model, HypoE mouse was reported to exhibit atherogenic Paigen diet-induced coronary atherosclerosis and myocardial infarction; however, the HypoE mice died too early to make possible investigation of cardiac remodeling. Therefore, we aimed to modify the HypoE mouse model to establish a novel model for ischemic cardiomyopathy caused by atherosclerotic lesions, which the ligation model does not exhibit.Methods and ResultsIn our study, the sustained Paigen diet for the HypoE mice was shortened to 7 or 10 days, allowing the mice to survive longer. The 7-day Paigen diet intervention starting when the mice were 8 weeks old was adequate to permit the mice to survive myocardial infarction. Our murine model, called the “modified HypoE mouse”, was maintained until 8 weeks, with a median survival period of 36 days, after the dietary intervention (male, n = 222). Echocardiography demonstrated that the fractional shortening 2 weeks after the Paigen diet (n = 14) significantly decreased compared with that just before the Paigen diet (n = 6) (31.4±11.9% vs. 54.4±2.6%, respectively, P<0.01). Coronary angiography revealed multiple diffuse lesions. Cardiac remodeling and fibrosis were identified by serial analyses of cardiac morphological features and mRNA expression levels in tissue factors such as MMP-2, MMP-9, TIMP-1, collagen-1, and TGF-β.ConclusionModified HypoE mice are a suitable model for ischemic cardiomyopathy with multiple diffuse lesions and may be considered as a novel and convenient model for investigations of cardiac remodeling on a highly atherogenic background. |
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