Chemerin-9, a potent agonist of chemerin receptor (ChemR23), prevents atherogenesis
-
- Kengo Sato
- Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
-
- Hayami Yoshizawa
- Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
-
- Tomomi Seki
- Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
-
- Remina Shirai
- Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
-
- Tomoyuki Yamashita
- Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
-
- Taisuke Okano
- Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
-
- Koichiro Shibata
- Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
-
- Miyu J. Wakamatsu
- Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
-
- Yusaku Mori
- Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
-
- Toshisuke Morita
- Department of Laboratory Medicine, Toho University Faculty of Medicine, Tokyo, Japan
-
- Taka-aki Matsuyama
- Department of Legal Medicine, Showa University School of Medicine, Tokyo, Japan
-
- Hatsue Ishibashi-Ueda
- Department of Pathology, National Cerebral and Cardiovascular Center, Osaka, Japan
-
- Tsutomu Hirano
- Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
-
- Takuya Watanabe
- Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
説明
<jats:title>Abstract</jats:title> <jats:p>Plasma levels of chemerin, an adipocytokine produced from the adipose tissues and liver, are associated with metabolic syndrome and coronary artery disease (CAD). Chemerin and its analog, chemerin-9, are known to bind to their receptor, ChemR23. However, whether chemerin and chemerin-9 affect atherogenesis remains to be elucidated. We investigated the expression of chemerin and ChemR23 in human coronary arteries and cultured human vascular cells. The effects of chemerin and chemerin-9 on atheroprone phenomena were assessed in human THP1 monocytes, human umbilical vein endothelial cells (HUVECs), and human aortic smooth muscle cells (HASMCs) and aortic lesions in Apoe−/− mice. In patients with CAD, a small amount of ChemR23, but not chemerin, was expressed within atheromatous plaques in coronary arteries. Chemerin and ChemR23 were expressed at high levels in THP1 monocytes, THP1-derived macrophages, and HUVECs; however, their expression in HASMCs was weak. Chemerin and chemerin-9 significantly suppressed the tumor necrosis factor-α (TNF-α)-induced mRNA expression of adhesion and pro-inflammatory molecules in HUVECs. Chemerin and chemerin-9 significantly attenuated the TNF-α-induced adhesion of THP1 monocytes to HUVECs and macrophage inflammatory phenotype. Chemerin and chemerin-9 suppressed oxidized low-density lipoprotein (oxLDL)-induced macrophage foam cell formation associated with down-regulation of CD36 and up-regulation of ATP-binding cassette transporter A1 (ABCA1). In HASMCs, chemerin and chemerin-9 significantly suppressed migration and proliferation without inducing apoptosis. In the Apoe−/− mice, a 4-week infusion of chemerin-9 significantly decreased the areas of aortic atherosclerotic lesions by reducing intraplaque macrophage and SMC contents. Our results indicate that chemerin-9 prevents atherosclerosis. Therefore, the development of chemerin analogs/ChemR23 agonists may serve as a novel therapeutic target for atherosclerotic diseases.</jats:p>
収録刊行物
-
- Clinical Science
-
Clinical Science 133 (16), 1779-1796, 2019-08
Portland Press Ltd.
- Tweet
詳細情報 詳細情報について
-
- CRID
- 1361975843377988608
-
- ISSN
- 14708736
- 01435221
-
- データソース種別
-
- Crossref
- KAKEN