This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Goligorsky, M. S. Articles by Brodsky, S. Search for Related Content PubMed PubMed Citation Articles by Goligorsky, M. S. Articles by Brodsky, S. Related Collections Type 2 diabetes Endothelium/vascular type/nitric oxide

(Hypertension. 2001;37:744.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Workshop: Endothelial Cell Dysfunction Leading to Diabetic Nephropathy

Focus on Nitric Oxide

Michael S. Goligorsky; Jun Chen; Sergey Brodsky

From the Departments of Medicine, Physiology, and Biophysics, and the Program on Biomedical Engineering, State University of New York, Stony Brook.

Correspondence to M. Goligorsky, Division of Nephrology and Hypertension, SUNY, Stony Brook, NY 11794-8152. E-mail mgoligorsky{at}mail.som.sunysb.edu

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.

Key Words: nitric oxide synthase • collagen • plasminogen • diabetes mellitus

This article has been cited by other articles:

				Y. Yuzawa, I. Niki, T. Kosugi, S. Maruyama, F. Yoshida, M. Takeda, Y. Tagawa, Y. Kaneko, T. Kimura, N. Kato, et al. Overexpression of Calmodulin in Pancreatic {beta} Cells Induces Diabetic Nephropathy J. Am. Soc. Nephrol., September 1, 2008; 19(9): 1701 - 1711. [Abstract] [Full Text] [PDF]

				H. Shi, D. Patschan, T. Epstein, M. S. Goligorsky, and J. Winaver Delayed recovery of renal regional blood flow in diabetic mice subjected to acute ischemic kidney injury Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1512 - F1517. [Abstract] [Full Text] [PDF]

				C. Temm and J. H. Dominguez Microcirculation: nexus of comorbidities in diabetes Am J Physiol Renal Physiol, August 1, 2007; 293(2): F486 - F493. [Abstract] [Full Text] [PDF]

				G. P. Fadini, S. Sartore, C. Agostini, and A. Avogaro Significance of Endothelial Progenitor Cells in Subjects With Diabetes Diabetes Care, May 1, 2007; 30(5): 1305 - 1313. [Full Text] [PDF]

				R. Komers, W. E. Schutzer, J. F. Reed, J. N. Lindsley, T. T. Oyama, D. C. Buck, S. L. Mader, and S. Anderson Altered Endothelial Nitric Oxide Synthase Targeting and Conformation and Caveolin-1 Expression in the Diabetic Kidney Diabetes, June 1, 2006; 55(6): 1651 - 1659. [Abstract] [Full Text] [PDF]

				A. Mezentsev, R. M. H. Merks, E. O'Riordan, J. Chen, N. Mendelev, M. S. Goligorsky, and S. V. Brodsky Endothelial microparticles affect angiogenesis in vitro: role of oxidative stress Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H1106 - H1114. [Abstract] [Full Text] [PDF]

				C. S. Wilcox and D. Gutterman Focus on oxidative stress in the cardiovascular and renal systems Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H3 - H6. [Full Text] [PDF]

				R. D. Moraes, G. Gioseffi, A. C. L. Nobrega, and E. Tibirica Effects of exercise training on the vascular reactivity of the whole kidney circulation in rabbits J Appl Physiol, August 1, 2004; 97(2): 683 - 688. [Abstract] [Full Text] [PDF]

				S. V. Brodsky, F. Zhang, A. Nasjletti, and M. S. Goligorsky Endothelium-derived microparticles impair endothelial function in vitro Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H1910 - H1915. [Abstract] [Full Text] [PDF]

				S. Clement, S. S. Braithwaite, M. F. Magee, A. Ahmann, E. P. Smith, R. G. Schafer, and I. B. Hirsch Management of Diabetes and Hyperglycemia in Hospitals Diabetes Care, February 1, 2004; 27(2): 553 - 591. [Full Text] [PDF]

				F. Locatelli, B. Canaud, K.-U. Eckardt, P. Stenvinkel, C. Wanner, and C. Zoccali The importance of diabetic nephropathy in current nephrological practice Nephrol. Dial. Transplant., September 1, 2003; 18(9): 1716 - 1725. [Abstract] [Full Text] [PDF]

				H. T. Yu Progression of Chronic Renal Failure Arch Intern Med, June 23, 2003; 163(12): 1417 - 1429. [Abstract] [Full Text] [PDF]

				L. H. Opie and H.-H. Parving Diabetic Nephropathy: Can Renoprotection Be Extrapolated to Cardiovascular Protection? Circulation, August 6, 2002; 106(6): 643 - 645. [Full Text] [PDF]

				B.-S. Kim, J. Chen, T. Weinstein, E. Noiri, and M. S. Goligorsky VEGF Expression in Hypoxia and Hyperglycemia: Reciprocal Effect on Branching Angiogenesis in Epithelial-Endothelial Co-Cultures J. Am. Soc. Nephrol., August 1, 2002; 13(8): 2027 - 2036. [Abstract] [Full Text] [PDF]

				M. S. Segal, A. Bihorac, and M. Koc Circulating endothelial cells: tea leaves for renal disease Am J Physiol Renal Physiol, July 1, 2002; 283(1): F11 - F19. [Abstract] [Full Text] [PDF]