| First Author | Birch CL | Year | 2016 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 311 |
| Issue | 1 | Pages | H125-36 |
| PubMed ID | 27199124 | Mgi Jnum | J:234776 |
| Mgi Id | MGI:5790871 | Doi | 10.1152/ajpheart.00592.2015 |
| Citation | Birch CL, et al. (2016) Sex dimorphisms of crossbridge cycling kinetics in transgenic hypertrophic cardiomyopathy mice. Am J Physiol Heart Circ Physiol 311(1):H125-36 |
| abstractText | Familial hypertrophic cardiomyopathy (HCM) is a disease of the sarcomere and may lead to hypertrophic, dilated, restrictive, and/or arrhythmogenic cardiomyopathy, congestive heart failure, or sudden cardiac death. We hypothesized that hearts from transgenic HCM mice harboring a mutant myosin heavy chain increase the energetic cost of contraction in a sex-specific manner. To do this, we assessed Ca(2+) sensitivity of tension and crossbridge kinetics in demembranated cardiac trabeculas from male and female wild-type (WT) and HCM hearts at an early time point (2 mo of age). We found a significant effect of sex on Ca(2+) sensitivity such that male, but not female, HCM mice displayed a decrease in Ca(2+) sensitivity compared with WT counterparts. The HCM transgene and sex significantly impacted the rate of force redevelopment by a rapid release-restretch protocol and tension cost by the ATPase-tension relationship. In each of these measures, HCM male trabeculas displayed a gain-of-function when compared with WT counterparts. In addition, cardiac remodeling measured by echocardiography, histology, morphometry, and posttranslational modifications demonstrated sex- and HCM-specific effects. In conclusion, female and male HCM mice display sex dimorphic crossbridge kinetics accompanied by sex- and HCM-dependent cardiac remodeling at the morphometric, histological, and cellular level. |
