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Cardiac-specific overexpression of caveolin-3 preserves t-tubular I Ca during heart failure in mice

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Cardiac-specific overexpression of caveolin-3 preserves t-tubular I Ca during heart failure in mice. / Kong, Cherrie H T; Bryant, Simon M; Watson, Judy J; Roth, David M; Patel, Hemal H; Cannell, Mark B; James, Andrew F; Orchard, Clive H.

In: Experimental Physiology, Vol. 104, No. 5, 01.05.2019, p. 654-666.

Research output: Contribution to journalArticle

Harvard

Kong, CHT, Bryant, SM, Watson, JJ, Roth, DM, Patel, HH, Cannell, MB, James, AF & Orchard, CH 2019, 'Cardiac-specific overexpression of caveolin-3 preserves t-tubular I Ca during heart failure in mice', Experimental Physiology, vol. 104, no. 5, pp. 654-666. https://doi.org/10.1113/EP087304

APA

Kong, C. H. T., Bryant, S. M., Watson, J. J., Roth, D. M., Patel, H. H., Cannell, M. B., ... Orchard, C. H. (2019). Cardiac-specific overexpression of caveolin-3 preserves t-tubular I Ca during heart failure in mice. Experimental Physiology, 104(5), 654-666. https://doi.org/10.1113/EP087304

Vancouver

Author

Kong, Cherrie H T ; Bryant, Simon M ; Watson, Judy J ; Roth, David M ; Patel, Hemal H ; Cannell, Mark B ; James, Andrew F ; Orchard, Clive H. / Cardiac-specific overexpression of caveolin-3 preserves t-tubular I Ca during heart failure in mice. In: Experimental Physiology. 2019 ; Vol. 104, No. 5. pp. 654-666.

Bibtex

@article{739845c4d69c42b1be916ca1257fc3c5,
title = "Cardiac-specific overexpression of caveolin-3 preserves t-tubular I Ca 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.",
keywords = "TAC, excitation-contraction coupling, t-tubules, caveolin-3, overexpression",
author = "Kong, {Cherrie H T} and Bryant, {Simon M} and Watson, {Judy J} and Roth, {David M} and Patel, {Hemal H} and Cannell, {Mark B} and James, {Andrew F} and Orchard, {Clive H}",
year = "2019",
month = "5",
day = "1",
doi = "10.1113/EP087304",
language = "English",
volume = "104",
pages = "654--666",
journal = "Experimental Physiology",
issn = "0958-0670",
publisher = "Wiley",
number = "5",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - Cardiac-specific overexpression of caveolin-3 preserves t-tubular I Ca during heart failure in mice

AU - Kong, Cherrie H T

AU - Bryant, Simon M

AU - Watson, Judy J

AU - Roth, David M

AU - Patel, Hemal H

AU - Cannell, Mark B

AU - James, Andrew F

AU - Orchard, Clive H

PY - 2019/5/1

Y1 - 2019/5/1

N2 - 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.

AB - 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.

KW - TAC

KW - excitation-contraction coupling

KW - t-tubules

KW - caveolin-3

KW - overexpression

UR - http://www.scopus.com/inward/record.url?scp=85063012986&partnerID=8YFLogxK

U2 - 10.1113/EP087304

DO - 10.1113/EP087304

M3 - Article

VL - 104

SP - 654

EP - 666

JO - Experimental Physiology

JF - Experimental Physiology

SN - 0958-0670

IS - 5

ER -