Circulating Ligands of the Receptor for Advanced Glycation End Products and the Soluble Form of the Receptor Modulate Cardiovascular Cell Apoptosis in Diabetes

Molecules

AndreasS. Triantafyllis¹  IoannisK. Rizos¹  Vasileos Salpeas¹  AngelosG. Rigopoulos¹  Erifili Hatziagelaki²  Anastasia Tsiavou²  Sahil Gupta³  Shehla Izhar³  JohnC. Marshall³  JamesN. Tsoporis³  ThomasG. Parker³ 

[1] Academic Department of Cardiology, Attikon University Hospital, University of Athens Medical School, 12462 Athens, Greece;Department of Internal Medicine, Research Institute and Diabetes Center, Attikon University Hospital, University of Athens Medical School, 124 62 Athens, Greece;Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, Unity Health Toronto, University of Toronto, Toronto, ON M5B 1T8, Canada;

关键词: S100 proteins;    diabetes;    receptor for advanced glycation end products;    apoptosis;   

DOI  :  10.3390/molecules25225235

来源: DOAJ

【 摘 要 】

We determined whether plasma concentrations of the receptor for advanced glycation end products (RAGE) and the soluble (s) form of RAGE (sRAGE) in healthy individuals and patients with type 2 diabetes (T2D) modulate vascular remodeling. Healthy individuals and patients with T2D were divided into two age groups: young = <35 years old or middle-aged (36–64 years old) and stratified based on normal glucose tolerance (NGT), impaired (IGT), and T2D. Plasma titers of sRAGE, the RAGE ligands, AGEs, S100B, S100A1, S100A6, and the apoptotic marker Fas ligand Fas(L) were measured by enzyme-linked immunosorbent assay (ELISA). The apoptotic potential of the above RAGE ligands and sRAGE were assessed in cultured adult rat aortic smooth muscle cells (ASMC). In NGT individuals, aging increased the circulating levels of AGEs and S100B and decreased sRAGE, S100A1 and S100A6. Middle-aged patients with T2D presented higher levels of circulating S100B, AGEs and FasL, but lower levels of sRAGE, S100A1 and S100A6 than individuals with NGT or IGT. Treatment of ASMC with either AGEs or S100B at concentrations detected in T2D patients increased markers of inflammation and apoptosis. Responses attenuated by concomitant administration of sRAGE. In middle-aged patients with T2D, lower circulating plasma levels of sRAGE may limit decoy and exogenous trapping of deleterious pro-apoptotic/pro-inflammatory RAGE ligands AGEs and S100B, increasing the risk for diabetic complications.

【 授权许可】

Unknown