Adropin Contributes to Anti-Atherosclerosis by Suppressing Monocyte-Endothelial Cell Adhesion and Smooth Muscle Cell Proliferation

Sato, Kengo; Yamashita, Tomoyuki; Shirai, Remina; Shibata, Koichiro; Okano, Taisuke; Yamaguchi, Maho; Mori, Yusaku; Hirano, Tsutomu; Watanabe, Takuya

doi:10.3390/ijms19051293

Open AccessArticle

Adropin Contributes to Anti-Atherosclerosis by Suppressing Monocyte-Endothelial Cell Adhesion and Smooth Muscle Cell Proliferation

by

Kengo Sato

^1,*,†,

Tomoyuki Yamashita

^1,†,

Remina Shirai

¹,

Koichiro Shibata

¹,

Taisuke Okano

¹,

Maho Yamaguchi

¹,

Yusaku Mori

²,

Tsutomu Hirano

²

and

Takuya Watanabe

¹

Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-City, Tokyo 192-0392, Japan

²

Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2018, 19(5), 1293; https://doi.org/10.3390/ijms19051293

Submission received: 1 April 2018 / Revised: 18 April 2018 / Accepted: 23 April 2018 / Published: 26 April 2018

(This article belongs to the Special Issue Pathomechanisms of Atherosclerosis. Part I)

Download

Browse Figures

Versions Notes

Abstract

Adropin, a peptide hormone expressed in liver and brain, is known to improve insulin resistance and endothelial dysfunction. Serum levels of adropin are negatively associated with the severity of coronary artery disease. However, it remains unknown whether adropin could modulate atherogenesis. We assessed the effects of adropin on inflammatory molecule expression and human THP1 monocyte adhesion in human umbilical vein endothelial cells (HUVECs), foam cell formation in THP1 monocyte-derived macrophages, and the migration and proliferation of human aortic smooth muscle cells (HASMCs) in vitro and atherogenesis in Apoe^−/− mice in vivo. Adropin was expressed in THP1 monocytes, their derived macrophages, HASMCs, and HUVECs. Adropin suppressed tumor necrosis factor α-induced THP1 monocyte adhesion to HUVECs, which was associated with vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 downregulation in HUVECs. Adropin shifted the phenotype to anti-inflammatory M2 rather than pro-inflammatory M1 via peroxisome proliferator-activated receptor γ upregulation during monocyte differentiation into macrophages. Adropin had no significant effects on oxidized low-density lipoprotein-induced foam cell formation in macrophages. In HASMCs, adropin suppressed the migration and proliferation without inducing apoptosis via ERK1/2 and Bax downregulation and phosphoinositide 3-kinase/Akt/Bcl2 upregulation. Chronic administration of adropin to Apoe^−/− mice attenuated the development of atherosclerotic lesions in the aorta, with reduced the intra-plaque monocyte/macrophage infiltration and smooth muscle cell content. Thus, adropin could serve as a novel therapeutic target in atherosclerosis and related diseases.

Keywords: atherosclerosis; endothelial cell; inflammation; macrophage; monocyte; smooth muscle cell

Graphical Abstract

Share and Cite

MDPI and ACS Style

Sato, K.; Yamashita, T.; Shirai, R.; Shibata, K.; Okano, T.; Yamaguchi, M.; Mori, Y.; Hirano, T.; Watanabe, T. Adropin Contributes to Anti-Atherosclerosis by Suppressing Monocyte-Endothelial Cell Adhesion and Smooth Muscle Cell Proliferation. Int. J. Mol. Sci. 2018, 19, 1293. https://doi.org/10.3390/ijms19051293

AMA Style

Sato K, Yamashita T, Shirai R, Shibata K, Okano T, Yamaguchi M, Mori Y, Hirano T, Watanabe T. Adropin Contributes to Anti-Atherosclerosis by Suppressing Monocyte-Endothelial Cell Adhesion and Smooth Muscle Cell Proliferation. International Journal of Molecular Sciences. 2018; 19(5):1293. https://doi.org/10.3390/ijms19051293

Chicago/Turabian Style

Sato, Kengo, Tomoyuki Yamashita, Remina Shirai, Koichiro Shibata, Taisuke Okano, Maho Yamaguchi, Yusaku Mori, Tsutomu Hirano, and Takuya Watanabe. 2018. "Adropin Contributes to Anti-Atherosclerosis by Suppressing Monocyte-Endothelial Cell Adhesion and Smooth Muscle Cell Proliferation" International Journal of Molecular Sciences 19, no. 5: 1293. https://doi.org/10.3390/ijms19051293

APA Style

Sato, K., Yamashita, T., Shirai, R., Shibata, K., Okano, T., Yamaguchi, M., Mori, Y., Hirano, T., & Watanabe, T. (2018). Adropin Contributes to Anti-Atherosclerosis by Suppressing Monocyte-Endothelial Cell Adhesion and Smooth Muscle Cell Proliferation. International Journal of Molecular Sciences, 19(5), 1293. https://doi.org/10.3390/ijms19051293

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Menu

Adropin Contributes to Anti-Atherosclerosis by Suppressing Monocyte-Endothelial Cell Adhesion and Smooth Muscle Cell Proliferation

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI