Toma Laura, Stancu Camelia Sorina, Sima Anca Volumnia
Lipidomics Department, Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, 8, B.P. Hasdeu Street, 050568 Bucharest, Romania.
Biomedicines. 2020 Dec 27;9(1):18. doi: 10.3390/biomedicines9010018.
Diabetes and its vascular complications affect an increasing number of people. This disease of epidemic proportion nowadays involves abnormalities of large and small blood vessels, all commencing with alterations of the endothelial cell (EC) functions. Cardiovascular diseases are a major cause of death and disability among diabetic patients. In diabetes, EC dysfunction (ECD) is induced by the pathological increase of glucose and by the appearance of advanced glycation end products (AGE) attached to the plasma proteins, including lipoproteins. AGE proteins interact with their specific receptors on EC plasma membrane promoting activation of signaling pathways, resulting in decreased nitric oxide bioavailability, increased intracellular oxidative and inflammatory stress, causing dysfunction and finally apoptosis of EC. Irreversibly glycated lipoproteins (AGE-Lp) were proven to have an important role in accelerating atherosclerosis in diabetes. The aim of the present review is to present up-to-date information connecting hyperglycemia, ECD and two classes of glycated Lp, glycated low-density lipoproteins and glycated high-density lipoproteins, which contribute to the aggravation of diabetes complications. We will highlight the role of dyslipidemia, oxidative and inflammatory stress and epigenetic risk factors, along with the specific mechanisms connecting them, as well as the new promising therapies to alleviate ECD in diabetes.
糖尿病及其血管并发症影响着越来越多的人。如今这种具有流行趋势的疾病涉及大血管和小血管的异常，所有这些都始于内皮细胞（EC）功能的改变。心血管疾病是糖尿病患者死亡和致残的主要原因。在糖尿病中，葡萄糖病理性增加以及与包括脂蛋白在内的血浆蛋白结合的晚期糖基化终产物（AGE）的出现会诱发内皮细胞功能障碍（ECD）。AGE蛋白与其在EC质膜上的特异性受体相互作用，促进信号通路的激活，导致一氧化氮生物利用度降低、细胞内氧化和炎症应激增加，从而引起EC功能障碍并最终导致其凋亡。不可逆糖化脂蛋白（AGE-Lp）被证明在加速糖尿病患者动脉粥样硬化方面起重要作用。本综述的目的是介绍有关高血糖、ECD以及两类糖化脂蛋白（糖化低密度脂蛋白和糖化高密度脂蛋白）的最新信息，这些因素会导致糖尿病并发症的加重。我们将强调血脂异常、氧化和炎症应激以及表观遗传风险因素的作用，以及将它们联系起来的具体机制，还有减轻糖尿病患者ECD的新的有前景的治疗方法。
