MRTF-A regulates proliferation and survival properties of pro-atherogenic macrophages

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  • An Jianbo
    Department of Biochemistry and Metabolic Science, Akita University Graduate School of Medicine Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University
  • Naruse Taeko
    Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University
  • Hinohara Kunihiko
    Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University
  • Soejima Yurie
    Department of Molecular Pathology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University
  • Sawabe Motoji
    Department of Molecular Pathology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University
  • Nakagawa Yasuaki
    Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine
  • Kuwahara Koichiro
    Department of Cardiovascular Medicine, Shinshu University School of Medicine
  • Kuba Keiji
    Department of Biochemistry and Metabolic Science, Akita University Graduate School of Medicine
  • Kimura Akinori
    Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University

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Other Title
  • MRTF-Aはマクロファージ機能を制御して動脈硬化形成に関わる

Abstract

<p>Atherosclerosis often results in high incidence of vascular occlusion and has been recognized as the major cause of coronary artery disease. We had previously reported that promoter polymorphism of myocardin-related transcription factor A (MRTF-A) is associated with coronary atherosclerosis. However, the contribution of MRTF-A to the development of atherosclerosis remains unclear. Macrophages are known to be important mediators of atherosclerosis. In this study, we found that MRTF-A was highly expressed in lesional macrophages in human carotid atherosclerotic plaque. To investigate the role of macrophagic MRTF-A in the pathogenesis of atherosclerosis, we generated ApoE null MRTF-A transgenic mice (ApoE−/−/MRTF-Atg/+), in which human MRTF-A was specifically overexpressed in monocytes/macrophages. We found that ApoE−/−/MRTF-Atg/+ aggravated atherosclerosis and accumulated prominent lesional macrophages in the aortic sinus. We also found that MRTF-A promoted proliferation of macrophages and mitigated apoptosis both in vitro and in vivo due to downregulation of the expression of cyclin-dependent kinase inhibitors. Taken together, our data indicated that MRTF-A contributes to the development of atherosclerosis by modulating functional properties of pro-atherogenic macrophages.</p>

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