Gender and aging in a transgenic mouse model of hypertrophic cardiomyopathy.
Mutations in the cardiac myosin heavy chain (MHC) can cause familial hypertrophic cardiomyopathy (FHC). A transgenic mouse model has been developed in which a missense (R403Q) allele and an actin-binding deletion in the alpha-MHC are expressed in the heart. We used an isovolumic left heart preparation to study the contractile characteristics of hearts from transgenic (TG) mice and their wild-type (WT) littermates. Both male and female TG mice developed left ventricular (LV) hypertrophy at 4 mo of age. LV hypertrophy was accompanied by LV diastolic dysfunction, but LV systolic function was normal and supranormal in the young TG females and males, respectively. At 10 mo of age, the females continued to present with LV concentric hypertrophy, whereas the males began to display LV dilation. In female TG mice at 10 mo of age, impaired LV diastolic function persisted without evidence of systolic dysfunction. In contrast, in 10-mo-old male TG mice, LV diastolic function worsened and systolic performance was impaired. Diminished coronary flow was observed in both 10-mo-old TG groups. These types of changes may contribute to the functional decompensation typically seen in hypertrophic cardiomyopathy. Collectively, these results further underscore the potential utility of this transgenic mouse model in elucidating pathogenesis of FHC.
Olsson
M C
MC
Department of Kinesiology and Applied Physiology, University of Colorado, Boulder 80309-0354, USA.
Palmer
B M
BM
Leinwand
L A
LA
Moore
R L
RL
D000375:Aging / Q000502:physiology*; D000818:Animals; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D003326:Coronary Circulation; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction; D018995:Myosin Heavy Chains / Q000235:genetics; D009929:Organ Size; D012727:Sex Characteristics; D018487:Ventricular Dysfunction, Left / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D017725:Ventricular Pressure
D018995:Myosin Heavy Chains