The Institute of Cardiovascular Sciences, Institute of Systems Biomedicine, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University Health Science Center, Xueyuan Road 38, Beijing 100191, China.
Department of Immunology, Peking University School of Basic Medical Science, Key Laboratory of Medical Immunology, Ministry of Health, Peking University Health Sciences Center, Xueyuan Road 38, Beijing 100191, China.
Cardiovasc Res. 2021 Jan 21;117(2):450-461. doi: 10.1093/cvr/cvaa011.
Eva-1 homologue 1 (Eva1a) is a novel protein involved in the regulation of cardiac remodelling and plaque stability, but little is known about its role in re-endothelialization and the development of atherosclerosis (AS). Thus, in the present study, we aimed to elucidate the function of Eva1a in re-endothelialization and AS.
Wire injuries of carotid and femoral arteries were established in Eva1a-/- mice. Eva1a-deficient mice were crossed with apolipoprotein E-/- (ApoE-/-) mice to evaluate AS development and re-endothelialization of carotid artery injuries. Denudation of the carotid artery at 3, 5, and 7 days was significantly aggravated in Eva1a-/- mice. The neointima of the femoral artery at 14 and 28 days was consequently exacerbated in Eva1a-/- mice. The area of atherosclerotic lesions was increased in Eva1a-/-ApoE-/- mice. To explore the underlying mechanisms, we performed transwell, scratch migration, cell counting kit-8, and bromodeoxyuridine assays using cultured human aorta endothelial cells (HAECs), which demonstrated that EVA1A promoted HAEC migration and proliferation. Proteomics revealed that the level of actin-related protein 2/3 complex subunit 1B (Arpc1b) was decreased, while Eva1a expression was absent. Arpc1b was found to be a downstream molecule of EVA1A by small interfering RNA transfection assay. Activation of Rac1 and Cdc42 GTPases was also regulated by EVA1A.
This study provides insights into anti-atherogenesis effects of Eva1a by promoting endothelium repair. Thus, Eva1a is a promising therapeutic target for AS.
Eva-1 同源物 1（Eva1a）是一种参与心脏重塑和斑块稳定性调节的新型蛋白，但关于其在再内皮化和动脉粥样硬化（AS）发展中的作用知之甚少。因此，本研究旨在阐明 Eva1a 在再内皮化和 AS 中的作用。
在 Eva1a-/-小鼠中建立颈动脉和股动脉的钢丝损伤模型。将 Eva1a 缺陷型小鼠与载脂蛋白 E-/-（ApoE-/-）小鼠杂交，以评估颈动脉损伤的 AS 发展和再内皮化情况。Eva1a-/-小鼠的颈动脉剥脱在 3、5 和 7 天明显加重。Eva1a-/-小鼠的股动脉内膜在 14 和 28 天也随之加剧。Eva1a-/-ApoE-/-小鼠的动脉粥样硬化病变面积增加。为了探索潜在机制，我们使用培养的人主动脉内皮细胞（HAEC）进行了 Transwell、划痕迁移、细胞计数试剂盒-8 和溴脱氧尿苷测定，结果表明 EVA1A 促进了 HAEC 的迁移和增殖。蛋白质组学显示肌动蛋白相关蛋白 2/3 复合物亚基 1B（Arpc1b）的水平降低，而 Eva1a 表达缺失。通过小干扰 RNA 转染实验发现 Arpc1b 是 EVA1A 的下游分子。EVA1A 还调节 Rac1 和 Cdc42 GTPase 的激活。
本研究通过促进内皮修复提供了 Eva1a 抗动脉粥样硬化作用的见解。因此，Eva1a 是 AS 有前途的治疗靶点。
