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Am J Physiol Heart Circ Physiol. 2016 Jul 1;311(1):H125-36. doi: 10.1152/ajpheart.00592.2015. Epub 2016 May 6.

Sex dimorphisms of crossbridge cycling kinetics in transgenic hypertrophic cardiomyopathy mice.

Author information

1
Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, Arizona; Department of Biomedical Engineering, University of Arizona, Tucson, Arizona;
2
Department of Physiology, University of Arizona, Tucson, Arizona; Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, Arizona;
3
Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, Arizona; Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona; and.
4
Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, Arizona; Department of Cellular and Molecular Medicine, University of Arizona, Tucson, Arizona.
5
Department of Physiology, University of Arizona, Tucson, Arizona; Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, Arizona; konhilas@arizona.edu.

Abstract

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.

KEYWORDS:

crossbridge cycle; sex/gender

PMID:
27199124
PMCID:
PMC4967209
DOI:
10.1152/ajpheart.00592.2015
[Indexed for MEDLINE]
Free PMC Article

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