Workshop: endothelial cell dysfunction leading to diabetic nephropathy : focus on nitric oxide.
Clinical manifestations of diabetic nephropathy are an expression of diabetic microangiopathy. This review revisits the previously proposed Steno hypothesis and advances our hypothesis that development of endothelial cell dysfunction represents a common pathophysiological pathway of diabetic complications. Specifically, the ability of glucose to scavenge nitric oxide is proposed as the initiation phase of endothelial dysfunction. Gradual accumulation of advanced glycated end products and induction of plasminogen activator inhibitor-1, resulting in the decreased expression of endothelial nitric oxide synthase and reduced generation of nitric oxide, are proposed to be pathophysiologically critical for the maintenance phase of endothelial dysfunction. The proposed conceptual shift toward the role of endothelial dysfunction in diabetic complications may provide new strategies for their prevention.
Departments of Medicine, Physiology, and Biophysics, and the Program on Biomedical Engineering, State University of New York, Stony Brook, USA. mgoligorsky@mail.som.sunysb.edu
M S
MS
Goligorsky
J
J
Chen
S
S
Brodsky
D000419:Albuminuria / Q000209:etiology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003925:Diabetic Angiopathies / Q000150:complications* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000209:etiology*; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000201:enzymology / Q000503:physiopathology*; D005947:Glucose / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000150:complications; D009569:Nitric Oxide / Q000172:deficiency / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism / Q000494:pharmacology
D017127:Glycation End Products, Advanced; D017395:Plasminogen Activator Inhibitor 1; D009569:Nitric Oxide; D000001:Calcimycin; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D005947:Glucose; D001920:Bradykinin