Aging and glycation promote erythrocyte phagocytosis by human endothelial cells: Potential impact in atherothrombosis under diabetic conditions
Aging and glycation promote erythrocyte phagocytosis by human endothelial cells: Potential impact in atherothrombosis under diabetic conditions
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DOI：
10.1016/j.atherosclerosis.2019.10.015
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发表时间：
2019-12-01
期刊：
影响因子：
5.3
通讯作者：
Meilhac, Olivier
中科院分区：
文献类型：
--
作者：
Catan, Aurelie;Turpin, Chloe;Meilhac, Olivier
背景和目标：2型糖尿病（T2 D）患者的动脉粥样硬化血栓形成斑块的特征在于增加的新血管形成和斑块内出血。红细胞的清除可以通过血管细胞进行。我们探讨了潜在的人内皮细胞结合和吞噬细胞在体外老年和/或糖化红细胞，以及从糖尿病patients.Methods获得的红细胞：新鲜的，老年人和老年人健康志愿者和T2 D患者的红细胞的结合和吞噬能力，以及对内皮细胞（活力，增殖和伤口愈合能力）的潜在功能后果进行了测试。免疫组化也进行了人类颈动脉粥样硬化血栓样本（从患者或没有T2 D）。结果：老化和糖化红细胞诱导磷脂酰丝氨酸（PS）暴露和氧化应激导致增强内皮细胞结合和吞噬。内皮细胞的吞噬作用在老年和糖化红细胞中比新鲜红细胞更明显。与健康红细胞相比，T2 D增强了吞噬作用。此外，暴露于老化红细胞与新鲜红细胞后，内皮伤口愈合潜力显著减弱。最后，我们表明红细胞和内皮细胞之间的相互作用及其潜在的吞噬作用可能发生在体内、动脉粥样硬化血栓形成条件下、新生血管和腔内皮衬里中。结论：内皮细胞可能在动脉粥样硬化血栓形成环境中的红细胞清除中发挥重要作用。在糖尿病条件下，红细胞糖化有利于其被内皮细胞吞噬，并可能参与内皮功能障碍，从而促进脆弱的动脉粥样硬化血栓斑块破裂。
Background and aims: Atherothrombotic plaques of type 2 diabetic (T2D) patients are characterized by an increased neovascularization and intraplaque hemorrhage. The clearance of erythrocytes may be carried out by vascular cells. We explored the potential of human endothelial cells to bind and phagocyte in vitro aged and/or glycated erythrocytes as well as erythrocytes obtained from diabetic patients.Methods: Fresh, aged and glycated-aged erythrocytes from healthy volunteers and T2D patients were tested for their binding and phagocytosis capacity as well as the potential functional consequences on endothelial cells (viability, proliferation and wound healing capacity). Immunohistochemistry was also performed in human carotid atherothrombotic samples (from patients with or without T2D).Results: Aging and glycation of erythrocytes induced phosphatidylserine (PS) exposure and oxidative stress leading to enhanced endothelial cell binding and engulfment. Phagocytosis by endothelial cells was more pronounced with aged and glycated erythrocytes than with fresh ones. Phagocytosis was enhanced with T2D versus healthy erythrocytes. Furthermore, endothelial wound healing potential was significantly blunted after exposure to glycated-aged versus fresh erythrocytes. Finally, we show that interactions between erythrocytes and endothelial cells and their potential phagocytosis may occur in vivo, in atherothrombotic conditions, in neovessels and in the luminal endothelial lining.Conclusions: Endothelial cells may play an important role in erythrocyte clearance in an atherothrombotic environment. Under diabetic conditions, erythrocyte glycation favors their engulfment by endothelial cells and may participate in endothelial dysfunction, thereby promoting vulnerable atherothrombotic plaques to rupture.