Fig. 3.

Accelerated heart failure and early mortality in αMHC-CryAB^R120G;beclin 1^+/− mice. (A) Cardiac function was monitored by serial echocardiography in nonsedated animals. αMHC-CryAB^R120G animals developed late-onset heart failure with the first signs of functional decline appearing at 9 months and development of heart failure by 12 months of age. In contrast, αMHC-CryAB^R120G;beclin 1^+/− mice manifested an accelerated disease course, with early signs of functional decline apparent at 6 months and terminal heart failure at 9 months. (B) Representative M-mode echocardiograms recorded in 9-month-old animals. (C) Declines in systolic performance are caused primarily by progressive increases in left ventricular internal dimension at end systole (LVIDs), with little change seen in end-diastolic diameter (LVIDd). By 12 months of age, the CryAB^R120G;Beclin 1^+/− animals had experienced 100% mortality. (D) Accumulation of RCAN1, indicative of calcineurin activation, as observed in αMHC-CryAB^R120G hearts at 9 months of age. RCAN1 levels were substantially higher in αMHC-CryAB^R120G;beclin 1^{+/ −} hearts.