ERK5 activation in macrophages promotes efferocytosis and inhibits atherosclerosis

Kyung Sun Heo, Hannah J. Cushman, Masashi Akaike, Chang Hoon Woo, Xin Wang, Xing Qiu, Keigi Fujiwara, Jun Ichi Abe

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background-Efferocytosis is a process by which dead and dying cells are removed by phagocytic cells. Efferocytosis by macrophages is thought to curb the progression of atherosclerosis, but the mechanistic insight of this process is lacking. Methods and Results-When macrophages were fed apoptotic cells or treated with pitavastatin in vitro, efferocytosisrelated signaling and phagocytic capacity were upregulated in an ERK5 activity-dependent manner. Macrophages isolated from macrophage-specific ERK5-null mice exhibited reduced efferocytosis and levels of gene and protein expression of efferocytosis-related molecules. When these mice were crossed with low-density lipoprotein receptor?/? mice and fed a high-cholesterol diet, atherosclerotic plaque formation was accelerated, and the plaques had more advanced and vulnerable morphology. Conclusions-Our results demonstrate that ERK5, which is robustly activated by statins, is a hub molecule that upregulates macrophage efferocytosis, thereby suppressing atherosclerotic plaque formation. Molecules that upregulate ERK5 and its signaling in macrophages may be good drug targets for suppressing cardiovascular diseases.

Original languageEnglish (US)
Pages (from-to)180-191
Number of pages12
JournalCirculation
Volume130
Issue number2
DOIs
StatePublished - Jul 8 2014

Fingerprint

Macrophage Activation
Atherosclerosis
Macrophages
Atherosclerotic Plaques
Up-Regulation
Hydroxymethylglutaryl-CoA Reductase Inhibitors
LDL Receptors
Phagocytes
Cardiovascular Diseases
Cholesterol
Diet
Gene Expression
Pharmaceutical Preparations
Proteins

Keywords

  • Atherosclerosis
  • Signal transduction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

ERK5 activation in macrophages promotes efferocytosis and inhibits atherosclerosis. / Heo, Kyung Sun; Cushman, Hannah J.; Akaike, Masashi; Woo, Chang Hoon; Wang, Xin; Qiu, Xing; Fujiwara, Keigi; Abe, Jun Ichi.

In: Circulation, Vol. 130, No. 2, 08.07.2014, p. 180-191.

Research output: Contribution to journalArticle

Heo, Kyung Sun ; Cushman, Hannah J. ; Akaike, Masashi ; Woo, Chang Hoon ; Wang, Xin ; Qiu, Xing ; Fujiwara, Keigi ; Abe, Jun Ichi. / ERK5 activation in macrophages promotes efferocytosis and inhibits atherosclerosis. In: Circulation. 2014 ; Vol. 130, No. 2. pp. 180-191.
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