Eva1a ameliorates atherosclerosis by promoting re-endothelialization of injured arteries via Rac1/Cdc42/Arpc1b

Abstract

Aims 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. Methods and results 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. Conclusion This study provides insights into anti-atherogenesis effects of Eva1a by promoting endothelium repair. Thus, Eva1a is a promising therapeutic target for AS.

p38α in macrophages aggravates arterial endothelium injury by releasing IL-6 through phosphorylating megakaryocytic leukemia 1

“…However, re-endothelialization effectively reduces the incidence of restenosis, and the incidence and mortality of CAD [ 9 , 10 ]. Our previous study shows that re-endothelialization plays an important role in atherosclerosis [ 11 ].…”

EVA1A Plays an Important Role by Regulating Autophagy in Physiological and Pathological Processes

“…Moreover, EVA1A deletion accelerated the development of AS, evidenced by the increased lesion formation and neointimal hyperplasia. Collectively, it can be deduced that EVA1A improves AS through increasing re-endothelialization of injured arteries by promoting ECs migration via Rac1/Cdc42/Arpc1b, which suggests that EVA1A is a potential therapeutic target for AS [70]. The above inference need to be further verified by the inhibitor of the ECs migration.…”

The Combined Contribution of Vascular Endothelial Cell Migration and Adhesion to Stent Re-endothelialization

“…Re-endothelialization is a complex mechanobiological process, which is modulated by the proliferation and migration of resident endothelial cells from uninjured intima (Evans et al, 2020;Li et al, 2021) and by the adhesion of circulating endothelial cells (Tesfamariam, 2016;Hu et al, 2019). Increased circulating endothelial cells in the peripheral blood have been reported in various pathologic conditions involving severe endothelial perturbation, including inflammatory disease, acute myocardial infarction, unstable angina, and critical limb ischemia (Makin et al, 2004;Lee et al, 2005).…”