Adropin Contributes to Anti-Atherosclerosis by Suppressing Monocyte-Endothelial Cell Adhesion and Smooth Muscle Cell Proliferation.
Adropin Contributes to Anti-Atherosclerosis by Suppressing Monocyte-Endothelial Cell Adhesion and Smooth Muscle Cell Proliferation.
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DOI：
10.3390/ijms19051293
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发表时间：
2018-04-26
影响因子：
5.6
通讯作者：
Watanabe T
中科院分区：
文献类型：
--
作者：
Sato K;Yamashita T;Shirai R;Shibata K;Okano T;Yamaguchi M;Mori Y;Hirano T;Watanabe T
Adropin 是一种在肝脏和大脑中表达的肽激素，已知可以改善胰岛素抵抗和内皮功能障碍。阿降品的血清水平与冠状动脉疾病的严重程度呈负相关。然而，阿德洛平是否可以调节动脉粥样硬化仍不清楚。我们评估了 adropin 对人脐静脉内皮细胞 (HUVEC) 中炎症分子表达和人 THP1 单核细胞粘附、THP1 单核细胞衍生巨噬细胞中泡沫细胞形成、体外人主动脉平滑肌细胞 (HASMC) 迁移和增殖以及体内 Apoe−/− 小鼠动脉粥样硬化形成的影响。 Adropin 在 THP1 单核细胞、其衍生的巨噬细胞、HASMC 和 HUVEC 中表达。 Adropin 抑制肿瘤坏死因子 α 诱导的 THP1 单核细胞对 HUVEC 的粘附，这与 HUVEC 中血管细胞粘附分子 1 和细胞间粘附分子 1 的下调有关。在单核细胞分化为巨噬细胞期间，Adropin 通过过氧化物酶体增殖物激活受体 γ 上调将表型转变为抗炎 M2，而不是促炎 M1。 Adropin 对氧化低密度脂蛋白诱导的巨噬细胞泡沫细胞形成没有显着影响。在 HASMC 中，adropin 通过 ERK1/2 和 Bax 下调以及磷酸肌醇 3-激酶/Akt/Bcl2 上调抑制迁移和增殖，而不诱导细胞凋亡。对Apoe−/−小鼠长期给予adropin可减轻主动脉动脉粥样硬化病变的发展，减少斑块内单核细胞/巨噬细胞浸润和平滑肌细胞含量。因此，adropin可以作为动脉粥样硬化及相关疾病的新治疗靶点。
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.
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影响因子：
29
作者：
Kumar KG;Trevaskis JL;Lam DD;Sutton GM;Koza RA;Chouljenko VN;Kousoulas KG;Rogers PM;Kesterson RA;Thearle M;Ferrante AW Jr;Mynatt RL;Burris TP;Dong JZ;Halem HA;Culler MD;Heisler LK;Stephens JM;Butler AA
通讯作者：
Butler AA
影响因子：
11.1
作者：
Rohwedder, Ina;Montanez, Eloi;Beckmann, Karsten;Bengtsson, Eva;Duner, Pontus;Nilsson, Jan;Soehnlein, Oliver;Faessler, Reinhard
通讯作者：
Faessler, Reinhard
DOI：
10.4149/bll_2016_020
发表时间：
2016-01-01
影响因子：
1.5
作者：
Akcilar, R.;Kocak, F. E.;Kokdasgil, H.
通讯作者：
Kokdasgil, H.
影响因子：
1.4
作者：
Altincik, Ayca;Sayin, Oya
通讯作者：
Sayin, Oya
影响因子：
4.3
作者：
Aydin, Suleyman;Kuloglu, Tuncay;Kendir, Yalcin
通讯作者：
Kendir, Yalcin