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Cellular and functional defects in a mouse model of heart failure.

Publication ,  Journal Article
Esposito, G; Santana, LF; Dilly, K; Cruz, JD; Mao, L; Lederer, WJ; Rockman, HA
Published in: Am J Physiol Heart Circ Physiol
December 2000

Heart failure and dilated cardiomyopathy develop in mice that lack the muscle LIM protein (MLP) gene (MLP(-/-)). The character and extent of the heart failure that occurs in MLP(-/-) mice were investigated using echocardiography and in vivo pressure-volume (P-V) loop measurements. P-V loop data were obtained with a new method for mice (sonomicrometry) using two pairs of orthogonal piezoelectric crystals implanted in the endocardial wall. Sonomicrometry revealed right-shifted P-V loops in MLP(-/-) mice, depressed systolic contractility, and additional evidence of heart failure. Cellular changes in MLP(-/-) mice were examined in isolated single cells using patch-clamp and confocal Ca(2+) concentration ([Ca(2+)]) imaging techniques. This cellular investigation revealed unchanged Ca(2+) currents and Ca(2+) spark characteristics but decreased intracellular [Ca(2+)] transients and contractile responses and a defect in excitation-contraction coupling. Normal cellular and whole heart function was restored in MLP(-/-) mice that express a cardiac-targeted transgene, which blocks the function of beta-adrenergic receptor (beta-AR) kinase-1 (betaARK1). These data suggest that, despite the persistent stimulus to develop heart failure in MLP(-/-) mice (i.e., loss of the structural protein MLP), downregulation and desensitization of the beta-ARs may play a pivotal role in the pathogenesis. Furthermore, this work suggests that the inhibition of betaARK1 action may prove an effective therapy for heart failure.

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Published In

Am J Physiol Heart Circ Physiol

DOI

ISSN

0363-6135

Publication Date

December 2000

Volume

279

Issue

6

Start / End Page

H3101 / H3112

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Ventricular Pressure
  • Transgenes
  • Systole
  • Receptors, Adrenergic, beta
  • Myocardium
  • Muscle Proteins
  • Muscle Fibers, Skeletal
  • Mice, Knockout
  • Mice
 

Citation

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MLA
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Esposito, G., Santana, L. F., Dilly, K., Cruz, J. D., Mao, L., Lederer, W. J., & Rockman, H. A. (2000). Cellular and functional defects in a mouse model of heart failure. Am J Physiol Heart Circ Physiol, 279(6), H3101–H3112. https://doi.org/10.1152/ajpheart.2000.279.6.H3101
Esposito, G., L. F. Santana, K. Dilly, J. D. Cruz, L. Mao, W. J. Lederer, and H. A. Rockman. “Cellular and functional defects in a mouse model of heart failure.Am J Physiol Heart Circ Physiol 279, no. 6 (December 2000): H3101–12. https://doi.org/10.1152/ajpheart.2000.279.6.H3101.
Esposito G, Santana LF, Dilly K, Cruz JD, Mao L, Lederer WJ, et al. Cellular and functional defects in a mouse model of heart failure. Am J Physiol Heart Circ Physiol. 2000 Dec;279(6):H3101–12.
Esposito, G., et al. “Cellular and functional defects in a mouse model of heart failure.Am J Physiol Heart Circ Physiol, vol. 279, no. 6, Dec. 2000, pp. H3101–12. Pubmed, doi:10.1152/ajpheart.2000.279.6.H3101.
Esposito G, Santana LF, Dilly K, Cruz JD, Mao L, Lederer WJ, Rockman HA. Cellular and functional defects in a mouse model of heart failure. Am J Physiol Heart Circ Physiol. 2000 Dec;279(6):H3101–H3112.

Published In

Am J Physiol Heart Circ Physiol

DOI

ISSN

0363-6135

Publication Date

December 2000

Volume

279

Issue

6

Start / End Page

H3101 / H3112

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Ventricular Pressure
  • Transgenes
  • Systole
  • Receptors, Adrenergic, beta
  • Myocardium
  • Muscle Proteins
  • Muscle Fibers, Skeletal
  • Mice, Knockout
  • Mice