| First Author | Kong CHT | Year | 2019 |
| Journal | Exp Physiol | Volume | 104 |
| Issue | 5 | Pages | 654-666 |
| PubMed ID | 30786093 | Mgi Jnum | J:295194 |
| Mgi Id | MGI:6458231 | Doi | 10.1113/EP087304 |
| Citation | Kong CHT, et al. (2019) Cardiac-specific overexpression of caveolin-3 preserves t-tubular ICa during heart failure in mice. Exp Physiol 104(5):654-666 |
| abstractText | NEW FINDINGS: What is the central question of this study? What is the cellular basis of the protection conferred on the heart by overexpression of caveolin-3 (Cav-3 OE) against many of the features of heart failure normally observed in vivo? What is the main finding and its importance? Cav-3 overexpression has little effect in normal ventricular myocytes but reduces cellular hypertrophy and preserves t-tubular ICa , but not local t-tubular Ca(2+) release, in heart failure induced by pressure overload in mice. Thus Cav-3 overexpression provides specific but limited protection following induction of heart failure, although other factors disrupt Ca(2+) 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 dilatation, 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(2+) 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(2+) current (ICa ) density was maintained. These data suggest that Cav-3 OE helps prevent hypertrophy and loss of t-tubular ICa following TAC, but that other factors disrupt local Ca(2+) release. |
