Endothelial Dysfunction in Diabetes Is Aggravated by Glycated Lipoproteins; Novel Molecular Therapies.
Endothelial Dysfunction in Diabetes Is Aggravated by Glycated Lipoproteins; Novel Molecular Therapies.
复制标题
DOI：
10.3390/biomedicines9010018
复制
发表时间：
2020-12-27
期刊：
影响因子：
4.7
通讯作者：
Sima AV
中科院分区：
文献类型：
--
作者：
Toma L;Stancu CS;Sima AV
糖尿病及其血管并发症影响越来越多的人。这种疾病的流行比例现在涉及异常的大血管和小血管，所有开始改变的内皮细胞（EC）的功能。心血管疾病是糖尿病患者死亡和残疾的主要原因。在糖尿病中，EC功能障碍（ECD）由葡萄糖的病理性增加和附着于血浆蛋白（包括脂蛋白）的晚期糖基化终产物（AGE）的出现诱导。AGE蛋白与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，导致EC功能障碍，最终导致EC凋亡。不可逆糖基化脂蛋白（AGE-Lp）在糖尿病动脉粥样硬化中起重要作用。本综述的目的是提供最新的信息连接高血糖症，ECD和两类糖化脂蛋白，糖化低密度脂蛋白和糖化高密度脂蛋白，这有助于糖尿病并发症的加重。我们将强调血脂异常，氧化和炎症应激和表观遗传危险因素的作用，沿着与它们相关的特定机制，以及缓解糖尿病ECD的新的有前途的治疗方法。
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.
登录
查看更多内容
影响因子：
39.3
作者：
Boren, Jan;Chapman, M. John;Ginsberg, Henry N.
通讯作者：
Ginsberg, Henry N.
影响因子：
7.7
作者：
Caballero, AE;Arora, S;Veves, A
通讯作者：
Veves, A
影响因子：
7.7
作者：
CURTISS, LK;WITZTUM, JL
通讯作者：
WITZTUM, JL
影响因子：
4.8
作者：
Balbi ME;Tonin FS;Mendes AM;Borba HH;Wiens A;Fernandez-Llimos F;Pontarolo R
通讯作者：
Pontarolo R
影响因子：
3.3
作者：
Alique M;Luna C;Carracedo J;Ramírez R
通讯作者：
Ramírez R