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1 Department of Kinesiology and Applied Physiology, 2 Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder 80309-0354; and 3 Cardiology Division, University of Colorado Health Sciences Center, Denver, Colorado 80262
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 
-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.
myosin; isovolumic; diastolic; systolic
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