Cardiac-specific overexpression of caveolin-3 preserves t-tubular ICa during heart failure in mice.

Abstract

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 Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ release.

• Authors: Cherrie H T Kong, Simon M Bryant, Judy J Watson, David M Roth, Hemal H Patel, Mark B Cannell, Andrew F James, Clive H Orchard
• Journal: Experimental physiology (Exp Physiol) Vol. 104 Issue 5 Pg. 654-666 (05 2019) ISSN: 1469-445X [Electronic] England
• PMID: 30786093 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2019 The Authors. Experimental Physiology Published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Chemical References

• Calcium Channels
• Cav3 protein, mouse
• Caveolin 3

Topics

• Animals
• Calcium Channels (metabolism)
• Calcium Signaling
• Cardiomegaly
• Caveolin 3 (genetics, metabolism)
• Constriction, Pathologic (physiopathology)
• Echocardiography
• Heart Failure (genetics, physiopathology)
• Heart Ventricles
• Male
• Mice
• Myocytes, Cardiac (metabolism)
• Pulmonary Circulation
• Sarcoplasmic Reticulum (metabolism)
• Stroke Volume
• Vasodilation