Open Access

CaMKII: The molecular villain that aggravates cardiovascular disease (Review)

  • Authors:
    • Peiying Zhang
  • View Affiliations

  • Published online on: Wednesday, January 11, 2017
  • DOI: 10.3892/etm.2017.4034
0

Abstract

Pathological remodeling of the myocardium is an integral part of the events that lead to heart failure (HF), which involves altered gene expression, disturbed signaling pathways and altered Ca2+ homeostasis and the players involved in this process. Of particular interest is the chronic activation of Ca2+/calmodulin‑dependent protein kinase II (CaMKII) isoforms in heart, which further aggravate the injury to myocardium. Expression and activity of CaMKII have been found to be elevated in various conditions of stressed myocardium and in different heart diseases in both animal models as well as heart patients. CaMKII is a signaling molecule that regulates many cellular pathways by phosphorylating several proteins involved in excitation‑contraction coupling and relaxation events in heart, cardiomyocyte apoptosis, transcriptional activation of genes related to cardiac hypertrophy, inflammation, and arrhythmias. CaMKII is activated by reactive oxygen species (ROS), which are elevated under conditions of ischemia‑reperfusion injury and in a cyclical manner, CaMKII in turn elevates ROS production. Both ROS and activated CaMKII increase Ca‑induced Ca release from sarcoplasmic reticulum, which leads to cardiomyocyte membrane depolarization and arrhythmias. These CaMKII‑mediated changes in heart ultimately culminate in dysfunctional myocardium and HF. Genetic studies in animal models clearly demonstrated that inactivation of CaMKII is protective against a variety of stress induced cardiac dysfunctions. Despite significant leaps in understanding the structural details of CaMKII, which is a very complicated and multimeric modular protein, currently there is no specific and potent inhibitor of this enzyme, that can be developed for therapeutic purposes.

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Print ISSN: 1792-0981
Online ISSN:1792-1015

2015 Impact Factor: 1.28
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APA
Zhang, P. (1899). CaMKII: The molecular villain that aggravates cardiovascular disease (Review). Experimental and Therapeutic Medicine, 0, 0-0. http://dx.doi.org/10.3892/etm.2017.4034
MLA
Zhang, P."CaMKII: The molecular villain that aggravates cardiovascular disease (Review)". Experimental and Therapeutic Medicine 0.0 (1899): 0-0.
Chicago
Zhang, P."CaMKII: The molecular villain that aggravates cardiovascular disease (Review)". Experimental and Therapeutic Medicine 0, no. 0 (1899): 0-0. http://dx.doi.org/10.3892/etm.2017.4034