CARDIAC‐SPECIFIC OVEREXPRESSION OF CAVEOLIN‐3 PRESERVES T‐TUBULAR ICa DURING HEART FAILURE IN MICE

New Findings

What is the central question of this study?

Overexpression of caveolin‐3 (Cav‐3 OE) appears to protect the heart against many of the features of heart failure (HF) normally observed in vivo. The present study investigates the cellular basis of this protection.

What is the main finding and its importance?

Cav‐3 OE has little effect in normal ventricular myocytes but reduces cellular hypertrophy and preserves t‐tubular I_Ca, but not local t‐tubular Ca release, in HF induced by pressure‐overload in mice. Thus Cav‐3 OE provides specific but limited protection following induction of HF, although other factors disrupt Ca release.

ABSTRACT

Caveolin‐3 (Cav‐3) is an 18 kDa protein that has been implicated in t‐tubule formation and function in cardiac ventricular myocytes. During cardiac hypertrophy and failure, Cav‐3 expression decreases, t‐tubule structure is disrupted and excitation‐contraction coupling (ECC) is impaired. Previous work has suggested that Cav‐3 overexpression (OE) is cardio‐protective, but the effect of Cav‐3 OE on these cellular changes is unknown. We therefore investigated whether Cav‐3 OE in mice is protective against the cellular effects of pressure overload induced by 8 weeks transverse aortic constriction (TAC). Cav‐3 OE mice developed cardiac dilation, decreased stroke volume and ejection fraction, and hypertrophy and pulmonary congestion in response to TAC. These changes were accompanied by cellular hypertrophy, a decrease in t‐tubule regularity and density and impaired local Ca release at the t‐tubules. However, the extent of cardiac and cellular hypertrophy was reduced in Cav‐3 OE compared to WT mice, and t‐tubular Ca current (I_Ca) density was maintained. These data suggest that Cav‐3 OE helps prevent hypertrophy and loss of t‐tubular I_Ca following TAC, but that other factors disrupt local Ca release.

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