Sex dimorphisms of crossbridge cycling kinetics in transgenic hypertrophic cardiomyopathy mice

Camille L. Birch, Samantha M. Behunin, Marissa A. Lopez-Pier, Christiane Danilo, Yulia Lipovka, Chandra Saripalli, Henk Granzier, John P. Konhilas

Research output: Contribution to journalArticle

4 Scopus citations

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 Ca2+ 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 Ca2+ sensitivity such that male, but not female, HCM mice displayed a decrease in Ca2+ 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.

Original languageEnglish (US)
Pages (from-to)H125-H136
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume311
Issue number1
DOIs
StatePublished - Jul 2016

Keywords

  • Crossbridge cycle
  • Sex/gender

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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