| First Author | Luo HC | Year | 2014 |
| Journal | J Huazhong Univ Sci Technolog Med Sci | Volume | 34 |
| Issue | 5 | Pages | 634-639 |
| PubMed ID | 25318870 | Mgi Jnum | J:308122 |
| Mgi Id | MGI:6726661 | Doi | 10.1007/s11596-014-1329-6 |
| Citation | Luo HC, et al. (2014) Age-related changes in familial hypertrophic cardiomyopathy phenotype in transgenic mice and humans. J Huazhong Univ Sci Technolog Med Sci 34(5):634-639 |
| abstractText | beta-myosin heavy chain mutations are the most frequently identified basis for hypertrophic cardiomyopathy (HCM). A transgenic mouse model (alphaMHC(403)) has been extensively used to study various mechanistic aspects of HCM. There is general skepticism whether mouse and human disease features are similar. Herein we compare morphologic and functional characteristics, and disease evolution, in a transgenic mouse and a single family with a MHC mutation. Ten male alphaMHC(403) transgenic mice (at t-5 weeks, -12 weeks, and -24 weeks) and 10 HCM patients from the same family with a beta-myosin heavy chain mutation were enrolled. Morphometric, conventional echocardiographic, tissue Doppler and strain analytic characteristics of transgenic mice and HCM patients were assessed. Ten male transgenic mice (alphaMHC(403)) were examined at ages -5 weeks, -12 weeks, and -24 weeks. In the transgenic mice, aging was associated with a significant increase in septal (0.59+/-0.06 vs. 0.64+/-0.05 vs. 0.69+/-0.11 mm, P<0.01) and anterior wall thickness (0.58+/-0.1 vs. 0.62+/-0.07 vs. 0.80+/-0.16 mm, P<0.001), which was coincident with a significant decrease in circumferential strain (-22%+/-4% vs. -20%+/-3% vs. -19%+/-3%, P=0.03), global longitudinal strain (-19%+/-3% vs. -17%+/-2% vs. -16%+/-3%, P=0.001) and E/A ratio (1.9+/-0.3 vs. 1.7+/-0.3 vs. 1.4+/-0.3, P=0.01). The HCM patients were classified into 1st generation (n=6; mean age 53+/-6 years), and 2nd generation (n=4; mean age 32+/-8 years). Septal thickness (2.2+/-0.9 vs. 1.4+/-0.1 cm, P<0.05), left atrial (LA) volume (62+/-16 vs. 41+/-5 mL, P=0.03), E/A ratio (0.77+/-0.21 vs. 1.1+/-0.1, P=0.01), E/e' ratio (25+/-10 vs. 12+/-2, P=0.03), global left ventricular (LV) strain (-14%+/-3% vs. -20%+/-3%, P=0.01) and global LV early diastolic strain rate (0.76+/-0.17 s(-1) vs. 1.3+/-0.2 s-1, P=0.01) were significantly worse in the older generation. In beta-myosin heavy chain mutations, transgenic mice and humans have similar progression in morphologic and functional abnormalities. The alphaMHC(403) transgenic mouse model closely recapitulates human disease. |
