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Cardiovascular & Hematological Disorders-Drug Targets
(Formerly Current Drug Targets - Cardiovascular & Hematological Disorders)
ISSN (Print): 1871-529X
ISSN (Online): 2212-4063
VOLUME: 14
ISSUE: 1
DOI: 10.2174/1871529X14666140401110841









Renal Endothelial Dysfunction in Diabetic Nephropathy

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Author(s): Huifang Cheng and Raymond C. Harris
Pages 22-33 (12)
Abstract:
Endothelial dysfunction has been posited to play an important role in the pathogenesis of diabetic nephropathy (DN). Due to the heterogeneity of endothelial cells (ECs), it is difficult to generalize about endothelial responses to diabetic stimuli. At present, there are limited techniques fordirectly measuring EC function in vivo, so diagnosis of endothelial disorders still largely depends on indirect assessment of mediators arising from EC injury. In the kidney microcirculation, both afferent and efferent arteries, arterioles and glomerular endothelial cells (GEnC) have all been implicated as targets of diabetic injury. Both hyperglycemia per se, as well as the metabolic consequences of glucose dysregulation, are thought to lead to endothelial cell dysfunction. In this regard, endothelial nitric oxide synthase (eNOS) plays a central role in EC dysfunction. Impaired eNOS activity can occur at numerous levels, including enzyme uncoupling, post-translational modifications, internalization and decreased expression. Reduced nitric oxide (NO) bioavailability exacerbates oxidative stress, further promoting endothelial dysfunction and injury. The injured ECs may then function as active signal transducers of metabolic, hemodynamic and inflammatory factors that modify the function and morphology of the vessel wall and interact with adjacent cells, which may activate a cascade of inflammatory and proliferative and profibrotic responses in progressive DN. Both pharmacological approaches and potential regenerative therapies hold promise for restoration of impaired endothelial cells in diabetic nephropathy.
Keywords:
diabetic nephropathy, endothelial cell, eNOS, heterogeneity, kidney, microvascular complication, nitric oxide, VEGF.
Affiliation:
Division of Nephrology, S3223 MCN, Vanderbilt University School of Medicine, and Nashville Veterans Affairs Hospital, Nashville, TN 37232, USA.