Cellular mechanisms and signalling pathways activated by high glucose and AGE-albumin in the aortic endothelium.
This review summarizes evidence on the effect of excess circulating glucose concentration and AGE-albumin on the aortic endothelial cells (ECs) phenotype, transport function, and expression of signalling molecules. The recent reports on the ECs dysfunction in diabetes are briefly reviewed, to provide a broader view on the link between ECs structural changes, functional alterations, and the underlying biochemical mechanisms. The original results emerging from streptozotocin-injected mice and human aortic endothelial cells grown in high (25 mM) glucose concentration are presented. Compared to physiological condition, in diabetes aortic ECs switch to a biosynthetic phenotype, present an increased number of caveolae, and enhance (by approximately 20%) transcytosis of AGE-albumin (AGE-Alb). In cultured ECs, 25 mM glucose induces approximately 2.6 fold increase in pSTAT-3 and pERK1 and approximately 1.8 fold increase in pERK2; further exposure to 5 microM AGE-Alb causes approximately 4.3 fold increase in pERK1/2 (vs. 5 mM glucose). Together, these data may explain the phenotypic change, enhanced permeability, and proliferation of aortic ECs in diabetic conditions.
Popov
Doina
D
Institute of Cellular Biology and Pathology N. Simionescu, Bucharest, Romania. doina.popov@icbp.ro
Simionescu
Maya
M
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D002199:Capillary Permeability / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D005947:Glucose / Q000378:metabolism*; D017127:Glycation End Products, Advanced; D006031:Glycosylation; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D017457:Receptors, Albumin / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D000093423:Glycated Serum Albumin
D017127:Glycation End Products, Advanced; D017457:Receptors, Albumin; D012709:Serum Albumin; D005947:Glucose; D000093423:Glycated Serum Albumin