Macro‐ and microvascular endothelial dysfunction in diabetes

Abstract

Endothelial cells, as well as their major products nitric oxide (NO) and prostacyclin, play a key role in the regulation of vascular homeostasis. Diabetes mellitus is an important risk factor for cardiovascular disease. Diabetes-induced endothelial dysfunction is a critical and initiating factor in the genesis of diabetic vascular complications. The present review focuses on both large blood vessels and the microvasculature. The endothelial dysfunction in diabetic macrovascular complications is characterized by reduced NO bioavailability, poorly compensated for by increased production of prostacyclin and/or endothelium-dependent hyperpolarizations, and increased production or action of endothelium-derived vasoconstrictors. The endothelial dysfunction of microvascular complications is primarily characterized by decreased release of NO, enhanced oxidative stress, increased production of inflammatory factors, abnormal angiogenesis, and impaired endothelial repair. In addition, non-coding RNAs (microRNAs) have emerged as participating in numerous cellular processes. Thus, this reviews pays special attention to microRNAs and their modulatory role in diabetes-induced vascular dysfunction. Some therapeutic strategies for preventing and restoring diabetic endothelial dysfunction are also highlighted.

Annexin A1 attenuates microvascular complications through restoration of Akt signalling in a murine model of type 1 diabetes

“…7). Similarly, therapeutic treatment with hrANXA1 (weeks [8][9][10][11][12][13] /Tyr 204 on ERK1/2 in both the heart and kidney (Fig. 7d, f), and Thr 180/182 on p38 in the heart (Fig.…”

“…Diabetic nephropathy is the primary cause of death in 21% of people with type 1 diabetes [4], and cardiovascular disease, which includes diabetic cardiomyopathy, accounts for 44% of all fatalities in type 1 diabetes [5]. Both pathologies are characterised by an impairment in function (kidney [proteinuria [6]], heart [impairment in systolic contractility [7]]) caused by local inflammation [8], endothelial dysfunction [9] and loss of survival pathways, the latter of which predisposes tissues to injury.…”

Targeting endothelial metaflammation to counteract diabesity cardiovascular risk: Current and perspective therapeutic options

“…Indeed, endothelial dysfunction -a condition in which the endothelium loses its physiological properties and shifts toward a vasoconstrictor, prothrombotic and pro-inflammatory state -is considered a major contributing factor in the etiology of diabetes-related microvascular diseases such as retinopathy, nephropathy, neuropathy, and impaired wound healing [9,10]. Moreover, endothelial dysfunction precedes the onset of macrovascular complications, mainly represented by atherosclerosis, which in diabetic patients is more rapid and more severe than in control population [10,11].…”

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“…A shift in the functions of the endothelium towards vasoconstriction, proinflammatory and prothrombic states characterizes the disruption of the normal performance of endothelial cells, leading to endothelial dysfunction, which is implicated in the pathogenesis of many diseases including diabetes [88]. The last three decades of the Steno hypothesis development and recent discoveries in the field advanced deep understanding of the pathogenesis, manifestations and sequelae of global dysfunction of the vascular endothelium in diabetes mellitus [89,90] activates PKC pathway resulting in increased oxidative stress [15,88]. A complex array of factors is associated with the pathogenesis of endothelial dysfunction [87].…”

“…Even that causality may be not very well established; multiple pathways leading to microvasculopathy, have been characterized. They include the endothelial nitric oxide synthase (eNOS) uncoupling and NO deficiency, oxidative and nitrosative stress, lysosomal membrane permeabilization and sirtuin 1 (SIRT1) deficiency, increased production of inflammatory factors, abnormal angiogenesis, premature senescence of endothelial and endothelial progenitor cells, and disintegration of endothelial glycocalyx have been characterized [90]. There is growing interest in the modulatory role of microRNAs in diabetes-induced vascular dysfunction [87,90].…”