title: Acto-myosin crossbridge kinetics in humans with coronary artery disease: influence of sex and diabetes mellitus.
abstract: Risk of heart failure (HF) is influenced by sex and diabetes mellitus (DM). To better understand these interactions, sub-epicardial myocardium from 26 patients with coronary artery disease (CAD) undergoing coronary bypass surgery was examined in vitro using sinusoidal length perturbation analysis at varying [Ca(2+)] to determine the viscoelastic properties of myofilaments related to acto-myosin crossbridge kinetics. Half of the patients had CAD only (four female, F-CAD; nine male, M-CAD), while the other half had both CAD and Type 2 DM (six F-DM; seven M-DM). At maximal and sub-maximal myofilament Ca(2+) activation there was a significant effect of sex and disease on frequency of maximum oscillatory work output during sinusoidal perturbation (P<0.05). Myofilaments from F-CAD produced oscillatory work at significantly higher frequencies compared with M-CAD, while myofilaments from F-DM and M-DM produced work at similar frequencies. Correspondingly, minimum viscoelastic stiffness at maximum Ca(2+) activation occurred at significantly higher frequencies in F-CAD (5.0+/-0.3 Hz) than M-CAD (3.3+/-0.3 Hz), but at similar frequencies in F-DM (3.7+/-0.3 Hz) and M-DM (4.3+/-0.2 Hz). Thus, sex influences acto-myosin crossbridge kinetics in myofilaments isolated from CAD patients. These sex-related differences were absent in DM, suggesting that differences in the properties of cardiac muscle contribute to reported sex differences in the incidence and mortality of HF in DM.
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, 89 Beaumont Avenue, Given C-207, Burlington, VT 05405-0068, USA. Naomi.Fukagawa@uvm.edu
authors.forename: Naomi K
authors.initials: NK
authors.lastname: Fukagawa
authors.forename: Bradley M
authors.initials: BM
authors.lastname: Palmer
authors.forename: William D
authors.initials: WD
authors.lastname: Barnes
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Leavitt
authors.forename: Frank P
authors.initials: FP
authors.lastname: Ittleman
authors.forename: Martin M
authors.initials: MM
authors.lastname: Lewinter
authors.forename: David W
authors.initials: DW
authors.lastname: Maughan
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology; D000205:Actomyosin / Q000378:metabolism*; D000328:Adult; D000368:Aged; D002118:Calcium / Q000378:metabolism; D003324:Coronary Artery Disease / Q000150:complications* / Q000378:metabolism*; D048909:Diabetes Complications / Q000378:metabolism*; D005260:Female; D006801:Humans; D007537:Isometric Contraction / Q000502:physiology; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D012727:Sex Characteristics
chemical_list: D000205:Actomyosin; D002118:Calcium