Cardiac hypertrophy and heart failure development through Gq and CaM kinase II signaling

Shikha Mishra, Haiyun Ling, Michael Grimm, Tong Zhang, Donald M Bers, Joan Heller Brown

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


The molecular events associated with the development of pathological hypertrophy have been shown to be stimulated through G-protein-coupled receptors that activate Gq signaling pathways in neonatal cardiomyocytes and in transgenic (TG) and knockout mice. We demonstrated that CaMKII, a multifunctional Ca 2+-regulated protein kinase, was activated through G-protein-coupled receptor and inositol trisphosphate-mediated Ca 2+ release and suggested that CaMKII was a downstream mediator of Gq-coupled hypertrophic signaling. This was supported by the demonstration of CaMKII activation by pressure overload [(transverse aortic constriction (TAC)] and induction of hypertrophy by TG CaMKII expression. CaMKII also phosphorylates Ca 2+ handling proteins including the ryanodine receptor (RyR2), phosphorylation of which markedly increases sarcoplasmic reticulum Ca2+ leak. Increased RyR2 phosphorylation is associated with heart failure development in CaMKII TG mice, and mice genetically deletedfor CaMKII (KO) have attenuated RyR2 phosphorylation, sarcoplasmic reticulum Ca 2+ leak, and heart failure development after long-term TAC. Genetic ablation of CaMKII also decreases development of heart failure in Gq TG mice and decreases infarct size, while improving functional recovery in mice subject to ischemia/reperfusion and preventing adverse remodeling after coronary artery occlusion. The underlying mechanisms are currently under study.

Original languageEnglish (US)
Pages (from-to)598-603
Number of pages6
JournalJournal of Cardiovascular Pharmacology
Issue number6
StatePublished - Dec 2010


  • CaMKII
  • GPCR
  • Heart failure
  • Hypertrophy
  • Ischemia/ reperfusion

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Cardiac hypertrophy and heart failure development through Gq and CaM kinase II signaling'. Together they form a unique fingerprint.

Cite this