Left ventricular dysfunction in murine models of heart failure and in failing human heart is associated with a selective decrease in the expression of caveolin-3

Ellina Cheskis Feiner; Paul Chung; Jean Francois Jasmin; Jin Zhang; Diana Whitaker-Menezes; Valerie Myers; Jianliang Song; Elizabeth W. Feldman; Hajime Funakoshi; Brent R. Degeorge; Rao V. Yelamarty; Walter J. Koch; Michael P. Lisanti; Charles F. McTiernan; Joseph Y. Cheung; Michael R. Bristow; Tung O. Chan; Arthur M. Feldman

doi:10.1016/j.cardfail.2010.10.008

Left ventricular dysfunction in murine models of heart failure and in failing human heart is associated with a selective decrease in the expression of caveolin-3

Ellina Cheskis Feiner, Paul Chung, Jean Francois Jasmin, Jin Zhang, Diana Whitaker-Menezes, Valerie Myers, Jianliang Song, Elizabeth W. Feldman, Hajime Funakoshi, Brent R. Degeorge, Rao V. Yelamarty, Walter J. Koch, Michael P. Lisanti, Charles F. McTiernan, Joseph Y. Cheung, Michael R. Bristow, Tung O. Chan, Arthur M. Feldman

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Caveolins are scaffolding proteins that are integral components of caveolae, flask-shaped invaginations in the membranes of all mammalian cells. Caveolin-1 and -2 are expressed ubiquitously, whereas caveolin-3 is found only in muscle. The role of caveolin-3 in heart muscle disease is controversial. Methods and Results: The present study was undertaken to assess the effects of left ventricular dysfunction on the expression of caveolin proteins using 2 well characterized models of murine heart failure and failing human heart. Transgenic mice with constitutive overexpression of A 1-adenosine receptor (A 1-TG) demonstrated cardiac dilatation and decreased left ventricular function at 10 weeks of age. This was accompanied by a marked decrease in caveolin-3 mRNA and protein levels compared with non-TG control mice. The change in caveolin-3 expression was selective, because levels of caveolin-1 and -2 did not change. Confocal imaging of myocytes isolated from A 1-TG mice demonstrated a loss of the plate-like appearance of T tubules. Caveolin-3 levels were also reduced in hearts from mice overexpressing tumor necrosis factor α. There was a direct relationship between caveolin-3 expression and fractional shortening in all mice that were studied (r = 0.65; P <.001). Although we could not demonstrate a significant decrease in caveolin-3 levels in failing human heart, we did find a direct correlation (r = 0.7; P <.05) between levels of caveolin-3 protein and Ca 2+-adenosine triphosphatase, a marker of the heart failure phenotype. Conclusions: These results suggest a relationship between left ventricular dysfunction and caveolin-3 levels and suggest that caveolin-3 may provide a novel target for heart failure therapy. © 2011 Elsevier Inc. All rights reserved.

Original language	English
Pages (from-to)	253-263
Number of pages	10
Journal	Journal of Cardiac Failure
Volume	17
Issue number	3
DOIs	https://doi.org/10.1016/j.cardfail.2010.10.008
Publication status	Published - Mar 2011

Keywords

adensine
Caveolin
heart failure
tumor necrosis factor

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10.1016/j.cardfail.2010.10.008

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Feiner, E. C., Chung, P., Jasmin, J. F., Zhang, J., Whitaker-Menezes, D., Myers, V., Song, J., Feldman, E. W., Funakoshi, H., Degeorge, B. R., Yelamarty, R. V., Koch, W. J., Lisanti, M. P., McTiernan, C. F., Cheung, J. Y., Bristow, M. R., Chan, T. O., & Feldman, A. M. (2011). Left ventricular dysfunction in murine models of heart failure and in failing human heart is associated with a selective decrease in the expression of caveolin-3. Journal of Cardiac Failure, 17(3), 253-263. https://doi.org/10.1016/j.cardfail.2010.10.008

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title = "Left ventricular dysfunction in murine models of heart failure and in failing human heart is associated with a selective decrease in the expression of caveolin-3",

abstract = "Background: Caveolins are scaffolding proteins that are integral components of caveolae, flask-shaped invaginations in the membranes of all mammalian cells. Caveolin-1 and -2 are expressed ubiquitously, whereas caveolin-3 is found only in muscle. The role of caveolin-3 in heart muscle disease is controversial. Methods and Results: The present study was undertaken to assess the effects of left ventricular dysfunction on the expression of caveolin proteins using 2 well characterized models of murine heart failure and failing human heart. Transgenic mice with constitutive overexpression of A 1-adenosine receptor (A 1-TG) demonstrated cardiac dilatation and decreased left ventricular function at 10 weeks of age. This was accompanied by a marked decrease in caveolin-3 mRNA and protein levels compared with non-TG control mice. The change in caveolin-3 expression was selective, because levels of caveolin-1 and -2 did not change. Confocal imaging of myocytes isolated from A 1-TG mice demonstrated a loss of the plate-like appearance of T tubules. Caveolin-3 levels were also reduced in hearts from mice overexpressing tumor necrosis factor α. There was a direct relationship between caveolin-3 expression and fractional shortening in all mice that were studied (r = 0.65; P <.001). Although we could not demonstrate a significant decrease in caveolin-3 levels in failing human heart, we did find a direct correlation (r = 0.7; P <.05) between levels of caveolin-3 protein and Ca 2+-adenosine triphosphatase, a marker of the heart failure phenotype. Conclusions: These results suggest a relationship between left ventricular dysfunction and caveolin-3 levels and suggest that caveolin-3 may provide a novel target for heart failure therapy. {\textcopyright} 2011 Elsevier Inc. All rights reserved.",

keywords = "adensine, Caveolin, heart failure, tumor necrosis factor",

author = "Feiner, {Ellina Cheskis} and Paul Chung and Jasmin, {Jean Francois} and Jin Zhang and Diana Whitaker-Menezes and Valerie Myers and Jianliang Song and Feldman, {Elizabeth W.} and Hajime Funakoshi and Degeorge, {Brent R.} and Yelamarty, {Rao V.} and Koch, {Walter J.} and Lisanti, {Michael P.} and McTiernan, {Charles F.} and Cheung, {Joseph Y.} and Bristow, {Michael R.} and Chan, {Tung O.} and Feldman, {Arthur M.}",

note = "HL 061690, NHLBI NIH HHS, United StatesHL 075443, NHLBI NIH HHS, United StatesHL 085503, NHLBI NIH HHS, United StatesHL 091799-01, NHLBI NIH HHS, United StatesHL 58672, NHLBI NIH HHS, United StatesHL 74854, NHLBI NIH HHS, United StatesP01 HL091799-01, NHLBI NIH HHS, United StatesR01 HL058672-02, NHLBI NIH HHS, United StatesR01 HL061690-02, NHLBI NIH HHS, United StatesR01 HL074854-01A2, NHLBI NIH HHS, United StatesR01 HL074854-06, NHLBI NIH HHS, United StatesR01 HL085503-01A1, NHLBI NIH HHS, United States",

year = "2011",

month = mar,

doi = "10.1016/j.cardfail.2010.10.008",

language = "English",

volume = "17",

pages = "253--263",

journal = "Journal of Cardiac Failure",

issn = "1071-9164",

publisher = "Elsevier BV",

number = "3",

}

Feiner, EC, Chung, P, Jasmin, JF, Zhang, J, Whitaker-Menezes, D, Myers, V, Song, J, Feldman, EW, Funakoshi, H, Degeorge, BR, Yelamarty, RV, Koch, WJ, Lisanti, MP, McTiernan, CF, Cheung, JY, Bristow, MR, Chan, TO & Feldman, AM 2011, 'Left ventricular dysfunction in murine models of heart failure and in failing human heart is associated with a selective decrease in the expression of caveolin-3', Journal of Cardiac Failure, vol. 17, no. 3, pp. 253-263. https://doi.org/10.1016/j.cardfail.2010.10.008

TY - JOUR

T1 - Left ventricular dysfunction in murine models of heart failure and in failing human heart is associated with a selective decrease in the expression of caveolin-3

AU - Feiner, Ellina Cheskis

AU - Chung, Paul

AU - Jasmin, Jean Francois

AU - Zhang, Jin

AU - Whitaker-Menezes, Diana

AU - Myers, Valerie

AU - Song, Jianliang

AU - Feldman, Elizabeth W.

AU - Funakoshi, Hajime

AU - Degeorge, Brent R.

AU - Yelamarty, Rao V.

AU - Koch, Walter J.

AU - Lisanti, Michael P.

AU - McTiernan, Charles F.

AU - Cheung, Joseph Y.

AU - Bristow, Michael R.

AU - Chan, Tung O.

AU - Feldman, Arthur M.

N1 - HL 061690, NHLBI NIH HHS, United StatesHL 075443, NHLBI NIH HHS, United StatesHL 085503, NHLBI NIH HHS, United StatesHL 091799-01, NHLBI NIH HHS, United StatesHL 58672, NHLBI NIH HHS, United StatesHL 74854, NHLBI NIH HHS, United StatesP01 HL091799-01, NHLBI NIH HHS, United StatesR01 HL058672-02, NHLBI NIH HHS, United StatesR01 HL061690-02, NHLBI NIH HHS, United StatesR01 HL074854-01A2, NHLBI NIH HHS, United StatesR01 HL074854-06, NHLBI NIH HHS, United StatesR01 HL085503-01A1, NHLBI NIH HHS, United States

PY - 2011/3

Y1 - 2011/3

N2 - Background: Caveolins are scaffolding proteins that are integral components of caveolae, flask-shaped invaginations in the membranes of all mammalian cells. Caveolin-1 and -2 are expressed ubiquitously, whereas caveolin-3 is found only in muscle. The role of caveolin-3 in heart muscle disease is controversial. Methods and Results: The present study was undertaken to assess the effects of left ventricular dysfunction on the expression of caveolin proteins using 2 well characterized models of murine heart failure and failing human heart. Transgenic mice with constitutive overexpression of A 1-adenosine receptor (A 1-TG) demonstrated cardiac dilatation and decreased left ventricular function at 10 weeks of age. This was accompanied by a marked decrease in caveolin-3 mRNA and protein levels compared with non-TG control mice. The change in caveolin-3 expression was selective, because levels of caveolin-1 and -2 did not change. Confocal imaging of myocytes isolated from A 1-TG mice demonstrated a loss of the plate-like appearance of T tubules. Caveolin-3 levels were also reduced in hearts from mice overexpressing tumor necrosis factor α. There was a direct relationship between caveolin-3 expression and fractional shortening in all mice that were studied (r = 0.65; P <.001). Although we could not demonstrate a significant decrease in caveolin-3 levels in failing human heart, we did find a direct correlation (r = 0.7; P <.05) between levels of caveolin-3 protein and Ca 2+-adenosine triphosphatase, a marker of the heart failure phenotype. Conclusions: These results suggest a relationship between left ventricular dysfunction and caveolin-3 levels and suggest that caveolin-3 may provide a novel target for heart failure therapy. © 2011 Elsevier Inc. All rights reserved.

AB - Background: Caveolins are scaffolding proteins that are integral components of caveolae, flask-shaped invaginations in the membranes of all mammalian cells. Caveolin-1 and -2 are expressed ubiquitously, whereas caveolin-3 is found only in muscle. The role of caveolin-3 in heart muscle disease is controversial. Methods and Results: The present study was undertaken to assess the effects of left ventricular dysfunction on the expression of caveolin proteins using 2 well characterized models of murine heart failure and failing human heart. Transgenic mice with constitutive overexpression of A 1-adenosine receptor (A 1-TG) demonstrated cardiac dilatation and decreased left ventricular function at 10 weeks of age. This was accompanied by a marked decrease in caveolin-3 mRNA and protein levels compared with non-TG control mice. The change in caveolin-3 expression was selective, because levels of caveolin-1 and -2 did not change. Confocal imaging of myocytes isolated from A 1-TG mice demonstrated a loss of the plate-like appearance of T tubules. Caveolin-3 levels were also reduced in hearts from mice overexpressing tumor necrosis factor α. There was a direct relationship between caveolin-3 expression and fractional shortening in all mice that were studied (r = 0.65; P <.001). Although we could not demonstrate a significant decrease in caveolin-3 levels in failing human heart, we did find a direct correlation (r = 0.7; P <.05) between levels of caveolin-3 protein and Ca 2+-adenosine triphosphatase, a marker of the heart failure phenotype. Conclusions: These results suggest a relationship between left ventricular dysfunction and caveolin-3 levels and suggest that caveolin-3 may provide a novel target for heart failure therapy. © 2011 Elsevier Inc. All rights reserved.

KW - adensine

KW - Caveolin

KW - heart failure

KW - tumor necrosis factor

U2 - 10.1016/j.cardfail.2010.10.008

DO - 10.1016/j.cardfail.2010.10.008

M3 - Article

C2 - 21362533

SN - 1071-9164

VL - 17

SP - 253

EP - 263

JO - Journal of Cardiac Failure

JF - Journal of Cardiac Failure

IS - 3

ER -

Left ventricular dysfunction in murine models of heart failure and in failing human heart is associated with a selective decrease in the expression of caveolin-3

Abstract

Keywords

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