Abstract
Increased oxidative stress and reduced nitric oxide (NO) bioavailability play a causal role in endothelial cell dysfunction occurring in the vasculature of diabetic patients. In this review, we summarized the molecular mechanisms underpinning diabetic endothelial and vascular dysfunction. In particular, we focused our attention on the complex interplay existing among NO, reactive oxygen species (ROS), and one crucial regulator of intracellular ROS production, p66Shc protein.
Highlights
Endothelial cells (ECs) synthesize and release different molecules that orchestrate metabolic, vascular, and cellular responses
Reactive oxygen species (ROS) as well as peroxynitrite oxidant produced by the reaction of superoxide anion with nitric oxide (NO), induce BH4 degradation leading to endothelial cell nitric oxide synthase (eNOS) uncoupling and to a reduction of the amount of endothelium-derived NO that is required for vascular relaxation and EC survival and proliferation [7]
MicroRNAs are small noncoding RNAs that regulate stability and translational inhibition of target messenger RNAs. miRNAs are involved in most biological processes, including proliferation, differentiation, development, migration, and apoptosis [11, 12]. miRNA dysregulation has been observed in the development of different diseases, including diabetes mellitus [13,14,15]
Summary
Endothelial cells (ECs) synthesize and release different molecules that orchestrate metabolic, vascular, and cellular responses. Nitric oxide (NO) is a key regulatory molecule of paramount importance for endothelial function and vascular tone relaxation [1, 2]. Reactive oxygen species (ROS), which include hydrogen peroxide (H2O2), superoxide anion (O2−), and hydroxyl radicals, play a pivotal role in endothelial and vascular function as well as in vascular tone constriction [4]. Physiological ROS levels play an important role as second messengers within the intracellular signaling. ROS as well as peroxynitrite oxidant produced by the reaction of superoxide anion with NO, induce BH4 degradation leading to eNOS uncoupling and to a reduction of the amount of endothelium-derived NO that is required for vascular relaxation and EC survival and proliferation [7]. We will show how the alteration of this network is one of the driving pathogenetic mechanisms underpinning diabetic vasculopathy and endothelial dysfunction
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