doi: 10.1161/01.RES.0000245453.09893.7f
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© 2006 American Heart Association, Inc.
Editorials |
Sphingosine-1-Phosphate
Waging a Battle in the Diabetic Blood Vessel
From the Division of Surgical Science, Department of Surgery, Columbia University Medical Center, New York, NY.
Correspondence to Ann Marie Schmidt, Columbia University Medical Center, 630 West 168th St, P&S 17-501, New York, NY 10032. E-mail ams11@columbia.edu
See related article, pages 731–739
Key Words: diabetes • vascular biology
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
A key question in unlocking the mystery of accelerated atherosclerosis that often accompanies types1 and 2 diabetes and leads to increased incidence and severity of heart attacks and strokes is, what are the precise biochemical and molecular signaling pathways that perturb the diabetic blood vessel leading to acceleration of vascular inflammation and atherosclerosis? Extensive evidence implicates elevated levels of glucose as a critical culprit in these phenomena. Beyond a critical threshold, it is apparent that increased glucose levels significantly exceed homeostatic requirements, and divert fundamental pathways leading to untoward nonphysiological effects in the cells.
Glucose may be dangerous, not solely because of its direct effects, but because of its long-term consequences. The studies of the Diabetes Control Clinical Trials (DCCT) and the Epidemiology of Diabetes Interventions and Complications Research (EDIC) Groups showed definitively that earlier rigorous glycemic control, despite eventual normalization of glucose levels compared with conventionally-treated type 1 diabetic subjects, exerted long-term protection against surrogate (carotid intima-media thickness) and frank end points (cardiovascular events and death) of cardiovascular disease.1–2 Why is the diabetic vessel so vulnerable to increased glucose? A plausible hypothesis is that it’s not just glucose; rather, excessive glucose is accompanied by clever accomplices in the pathways leading to irreversible vascular injury, some of which may be directly influenced by adverse signals emitted by hyperglycemia. For example, the nonenzymatic glycation and oxidation of proteins and lipids results in the generation of Advanced Glycation Endproducts (AGEs), key signaling species that perturb endothelium, smooth muscle cells and monocytes to
Related Article:
Circ. Res. 2006 99: 731-739.