Consequences of pressure overload on sarcomere protein mutation-induced XXXX .

@entity712 @entity101 @entity19 @entity1283 @entity1184 @entity12752 @entity205 @entity59417 @entity1121
BACKGROUND: Whether ventricular remodeling from @entity1121 ( @entity1121 ), systemic @entity101 , or other pathologies arises through a common signaling pathway or through independent molecular mechanisms is unknown. To study this, we assessed @entity1283 in a @entity19 model of @entity1121 subjected to increased left ventricular (LV) load. METHODS AND RESULTS: Transverse aortic banding of @entity19 with or without an @entity59417 cardiac myosin heavy chain mutation (alphaMHC403/+) produced similarly elevated LV pressures (120+/-30 versus 112+/-14 mm Hg; P=NS). No @entity19 developed @entity712 , and mortality (26% alphaMHC403/+, 35% wild-type) was comparable. Load-induced @entity1184 was identical in banded 129SvEv alphaMHC403/+ @entity19 (LV anterior wall [LVAW]=1.28+/-0.11) and 129SvEv wild-type @entity19 (LVAW=1.29+/-0.11 mm; P=NS). Genetically outbred @entity12752 ( @entity12752 ) alphaMHC403/+ @entity19 showed only mildly exaggerated @entity1184 in response to aortic banding ( @entity12752 alphaMHC403/+ LVAW=1.30+/-0.13 mm; @entity12752 wild-type LVAW=1.17+/-0.15 mm; P=0.03), suggesting some effect from a @entity12752 genetic locus that modifies @entity1184 induced by the cardiac MHC @entity59417 mutation. Histopathology and molecular markers of @entity1184 were comparable in all banded 129SvEv or @entity12752 @entity19 . Banded alphaMHC403/+ @entity19 had potential for greater @entity1184 , because @entity205 treatment markedly augmented @entity1184 . CONCLUSIONS: The uniform @entity1184 response to increased ventricular load in wild-type and alphaMHC403/+ @entity19 indicates independent cardiac remodeling pathways and predicts that coexistent @entity101 and @entity1121 should not profoundly exacerbate @entity1283 . In contrast, sarcomere mutation and @entity205 -mediated calcineurin inhibition stimulate a shared @entity1184 signaling pathway. Defining distinct signaling pathways that trigger myocyte growth should help to tailor therapies for @entity1283 .
