CaMKII, 'jack of all trades' in inflammation during cardiac ischemia/reperfusion injury

Wenjia Zhang; Erdan Dong; Junxia Zhang; Yan Zhang

doi:10.1016/j.yjmcc.2023.10.003

CaMKII, 'jack of all trades' in inflammation during cardiac ischemia/reperfusion injury

J Mol Cell Cardiol. 2023 Nov:184:48-60. doi: 10.1016/j.yjmcc.2023.10.003. Epub 2023 Oct 7.

Authors

Wenjia Zhang¹, Erdan Dong², Junxia Zhang³, Yan Zhang⁴

Affiliations

¹ State Key Laboratory of Vascular Homeostasis and Remodeling, Institute of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China.
² Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China; Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing 100191, China; Haihe Laboratory of Cell Ecosystem, Beijing 100191, China.
³ Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China; Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing 100191, China; Haihe Laboratory of Cell Ecosystem, Beijing 100191, China. Electronic address: zhangjunxia@pku.edu.cn.
⁴ State Key Laboratory of Vascular Homeostasis and Remodeling, Institute of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China. Electronic address: zhangyan9876@pku.edu.cn.

PMID: 37813179
DOI: 10.1016/j.yjmcc.2023.10.003

Abstract

Myocardial infarction and revascularization cause cardiac ischemia/reperfusion (I/R) injury featuring cardiomyocyte death and inflammation. The Ca²⁺/calmodulin dependent protein kinase II (CaMKII) family are serine/ threonine protein kinases that are involved in I/R injury. CaMKII exists in four different isoforms, α, β, γ, and δ. In the heart, CaMKII-δ is the predominant isoform，with multiple splicing variants, such as δB, δC and δ9. During I/R, elevated intracellular Ca²⁺ concentrations and reactive oxygen species activate CaMKII. In this review, we summarized the regulation and function of CaMKII in multiple cell types including cardiomyocytes, endothelial cells, and macrophages during I/R. We conclude that CaMKII mediates inflammation in the microenvironment of the myocardium, resulting in cell dysfunction, elevated inflammation, and cell death. However, different CaMKII-δ variants exhibit distinct or even opposite functions. Therefore, reagents/approaches that selectively target specific CaMKII isoforms and variants are needed for evaluating and counteracting the exact role of CaMKII in I/R injury and developing effective treatments against I/R injury.

Keywords: Calcium-calmodulin-dependent protein kinase type 2; Cardiac ischemia reperfusion injury; Cell death; Inflammation.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
Endothelial Cells / metabolism
Humans
Myocardial Infarction* / metabolism
Myocardial Reperfusion Injury* / metabolism
Myocytes, Cardiac / metabolism
Protein Isoforms / metabolism

Substances

Calcium-Calmodulin-Dependent Protein Kinase Type 2
Protein Isoforms