Title:Renal Endothelial Dysfunction in Diabetic Nephropathy
Volume: 14
Issue: 1
Author(s): Huifang Cheng and Raymond C. Harris
Affiliation:
Keywords:
diabetic nephropathy, endothelial cell, eNOS, heterogeneity, kidney, microvascular complication, nitric oxide,
VEGF.
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.
