Disruption of adenylyl cyclase type V does not rescue the phenotype of cardiac-specific overexpression of G αq protein-induced cardiomyopathy

Valeriy Timofeyev, Cliff A. Porter, Dipika Tuteja, Hong Qiu, Ning Li, Tong Tang, Anil Singapuri, Pyung Lim Han, Javier E Lopez, H. Kirk Hammond, Nipavan Chiamvimonvat

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Adenylyl cyclase (AC) is the principal effector molecule in the β-adrenergic receptor pathway. AC V and AC VI are the two predominant isoforms in mammalian cardiac myocytes. The disparate roles among AC isoforms in cardiac hypertrophy and progression to heart failure have been under intense investigation. Specifically, the salutary effects resulting from the disruption of AC V have been established in multiple models of cardiomyopathy. It has been proposed that a continual activation of AC V through elevated levels of protein kinase C could play an integral role in mediating a hypertrophic response leading to progressive heart failure. Elevated protein kinase C is a common finding in heart failure and was demonstrated in murine cardiomyopathy from cardiac-specific overexpression of G αq protein. Here we assessed whether the disruption of AC V expression can improve cardiac function, limit electrophysiological remodeling, or improve survival in the G αq mouse model of heart failure. We directly tested the effects of gene-targeted disruption of AC V in transgenic mice with cardiac-specific overexpression of G αq protein using multiple techniques to assess the survival, cardiac function, as well as structural and electrical remodeling. Surprisingly, in contrast to other models of cardiomyopathy, AC V disruption did not improve survival or cardiac function, limit cardiac chamber dilation, halt hypertrophy, or prevent electrical remodeling in G αq transgenic mice. In conclusion, unlike other established models of cardiomyopathy, disrupting AC V expression in the G αq mouse model is insufficient to overcome several parallel pathophysiological processes leading to progressive heart failure.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume299
Issue number5
DOIs
StatePublished - Nov 2010

Fingerprint

Cardiomyopathies
Phenotype
Heart Failure
Proteins
Atrial Remodeling
Adenylyl Cyclases
Protein Kinase C
Transgenic Mice
Protein Isoforms
Cardiomegaly
adenylyl cyclase type V
Cardiac Myocytes
Adrenergic Receptors
Hypertrophy
Dilatation
Genes

Keywords

  • Action potential
  • Hypertrophy
  • Mouse cardiac myocyte
  • Protein kinase C

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Disruption of adenylyl cyclase type V does not rescue the phenotype of cardiac-specific overexpression of G αq protein-induced cardiomyopathy. / Timofeyev, Valeriy; Porter, Cliff A.; Tuteja, Dipika; Qiu, Hong; Li, Ning; Tang, Tong; Singapuri, Anil; Han, Pyung Lim; Lopez, Javier E; Hammond, H. Kirk; Chiamvimonvat, Nipavan.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 299, No. 5, 11.2010.

Research output: Contribution to journalArticle

Timofeyev, Valeriy ; Porter, Cliff A. ; Tuteja, Dipika ; Qiu, Hong ; Li, Ning ; Tang, Tong ; Singapuri, Anil ; Han, Pyung Lim ; Lopez, Javier E ; Hammond, H. Kirk ; Chiamvimonvat, Nipavan. / Disruption of adenylyl cyclase type V does not rescue the phenotype of cardiac-specific overexpression of G αq protein-induced cardiomyopathy. In: American Journal of Physiology - Heart and Circulatory Physiology. 2010 ; Vol. 299, No. 5.
@article{12bb1a1074dd4fbda24b1bfd5044d909,
title = "Disruption of adenylyl cyclase type V does not rescue the phenotype of cardiac-specific overexpression of G αq protein-induced cardiomyopathy",
abstract = "Adenylyl cyclase (AC) is the principal effector molecule in the β-adrenergic receptor pathway. AC V and AC VI are the two predominant isoforms in mammalian cardiac myocytes. The disparate roles among AC isoforms in cardiac hypertrophy and progression to heart failure have been under intense investigation. Specifically, the salutary effects resulting from the disruption of AC V have been established in multiple models of cardiomyopathy. It has been proposed that a continual activation of AC V through elevated levels of protein kinase C could play an integral role in mediating a hypertrophic response leading to progressive heart failure. Elevated protein kinase C is a common finding in heart failure and was demonstrated in murine cardiomyopathy from cardiac-specific overexpression of G αq protein. Here we assessed whether the disruption of AC V expression can improve cardiac function, limit electrophysiological remodeling, or improve survival in the G αq mouse model of heart failure. We directly tested the effects of gene-targeted disruption of AC V in transgenic mice with cardiac-specific overexpression of G αq protein using multiple techniques to assess the survival, cardiac function, as well as structural and electrical remodeling. Surprisingly, in contrast to other models of cardiomyopathy, AC V disruption did not improve survival or cardiac function, limit cardiac chamber dilation, halt hypertrophy, or prevent electrical remodeling in G αq transgenic mice. In conclusion, unlike other established models of cardiomyopathy, disrupting AC V expression in the G αq mouse model is insufficient to overcome several parallel pathophysiological processes leading to progressive heart failure.",
keywords = "Action potential, Hypertrophy, Mouse cardiac myocyte, Protein kinase C",
author = "Valeriy Timofeyev and Porter, {Cliff A.} and Dipika Tuteja and Hong Qiu and Ning Li and Tong Tang and Anil Singapuri and Han, {Pyung Lim} and Lopez, {Javier E} and Hammond, {H. Kirk} and Nipavan Chiamvimonvat",
year = "2010",
month = "11",
doi = "10.1152/ajpheart.01208.2009",
language = "English (US)",
volume = "299",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "5",

}

TY - JOUR

T1 - Disruption of adenylyl cyclase type V does not rescue the phenotype of cardiac-specific overexpression of G αq protein-induced cardiomyopathy

AU - Timofeyev, Valeriy

AU - Porter, Cliff A.

AU - Tuteja, Dipika

AU - Qiu, Hong

AU - Li, Ning

AU - Tang, Tong

AU - Singapuri, Anil

AU - Han, Pyung Lim

AU - Lopez, Javier E

AU - Hammond, H. Kirk

AU - Chiamvimonvat, Nipavan

PY - 2010/11

Y1 - 2010/11

N2 - Adenylyl cyclase (AC) is the principal effector molecule in the β-adrenergic receptor pathway. AC V and AC VI are the two predominant isoforms in mammalian cardiac myocytes. The disparate roles among AC isoforms in cardiac hypertrophy and progression to heart failure have been under intense investigation. Specifically, the salutary effects resulting from the disruption of AC V have been established in multiple models of cardiomyopathy. It has been proposed that a continual activation of AC V through elevated levels of protein kinase C could play an integral role in mediating a hypertrophic response leading to progressive heart failure. Elevated protein kinase C is a common finding in heart failure and was demonstrated in murine cardiomyopathy from cardiac-specific overexpression of G αq protein. Here we assessed whether the disruption of AC V expression can improve cardiac function, limit electrophysiological remodeling, or improve survival in the G αq mouse model of heart failure. We directly tested the effects of gene-targeted disruption of AC V in transgenic mice with cardiac-specific overexpression of G αq protein using multiple techniques to assess the survival, cardiac function, as well as structural and electrical remodeling. Surprisingly, in contrast to other models of cardiomyopathy, AC V disruption did not improve survival or cardiac function, limit cardiac chamber dilation, halt hypertrophy, or prevent electrical remodeling in G αq transgenic mice. In conclusion, unlike other established models of cardiomyopathy, disrupting AC V expression in the G αq mouse model is insufficient to overcome several parallel pathophysiological processes leading to progressive heart failure.

AB - Adenylyl cyclase (AC) is the principal effector molecule in the β-adrenergic receptor pathway. AC V and AC VI are the two predominant isoforms in mammalian cardiac myocytes. The disparate roles among AC isoforms in cardiac hypertrophy and progression to heart failure have been under intense investigation. Specifically, the salutary effects resulting from the disruption of AC V have been established in multiple models of cardiomyopathy. It has been proposed that a continual activation of AC V through elevated levels of protein kinase C could play an integral role in mediating a hypertrophic response leading to progressive heart failure. Elevated protein kinase C is a common finding in heart failure and was demonstrated in murine cardiomyopathy from cardiac-specific overexpression of G αq protein. Here we assessed whether the disruption of AC V expression can improve cardiac function, limit electrophysiological remodeling, or improve survival in the G αq mouse model of heart failure. We directly tested the effects of gene-targeted disruption of AC V in transgenic mice with cardiac-specific overexpression of G αq protein using multiple techniques to assess the survival, cardiac function, as well as structural and electrical remodeling. Surprisingly, in contrast to other models of cardiomyopathy, AC V disruption did not improve survival or cardiac function, limit cardiac chamber dilation, halt hypertrophy, or prevent electrical remodeling in G αq transgenic mice. In conclusion, unlike other established models of cardiomyopathy, disrupting AC V expression in the G αq mouse model is insufficient to overcome several parallel pathophysiological processes leading to progressive heart failure.

KW - Action potential

KW - Hypertrophy

KW - Mouse cardiac myocyte

KW - Protein kinase C

UR - http://www.scopus.com/inward/record.url?scp=78249284074&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78249284074&partnerID=8YFLogxK

U2 - 10.1152/ajpheart.01208.2009

DO - 10.1152/ajpheart.01208.2009

M3 - Article

C2 - 20709863

AN - SCOPUS:78249284074

VL - 299

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 5

ER -