Endothelium as a Therapeutic Target in Diabetes Mellitus: From Basic Mechanisms to Clinical Practice

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Author(s): Anastasios Tentolouris, Ioanna Eleftheriadou, Evangelia Tzeravini, Dimitrios Tsilingiris, Stavroula A. Paschou, Gerasimos Siasos, Nikolaos Tentolouris*.

Journal Name: Current Medicinal Chemistry

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Abstract:

Endothelium plays an essential role in human homeostasis by regulating arterial blood pressure, distributing nutrients and hormones as well as providing a smooth surface that modulates coagulation, fibrinolysis and inflammation. Endothelial dysfunction is present in diabetes mellitus (DM) and contributes to the development and progression of macrovascular disease, while it is also associated with most of the microvascular complications such as diabetic retinopathy, nephropathy and neuropathy. Hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia are the main factors involved. Regarding antidiabetic medication, metformin, gliclazide, pioglitazone, exenatide and dapagliflozin exert a beneficial effect on endothelial function (EF); the other sulfonylureas, dipeptidyl peptidase- 4 inhibitors and liraglutide have a neutral effect, while studies examining the effect of insulin analogues, empagliflozin and canagliflozin on EF are limited. In terms of lipid-lower medication, statins improve EF in subjects with DM, whereas data from short-term trials suggest that fenofibrate improves EF; ezetimibe also improves EF but further studies are required in people with DM. The effect of acetylsalicylic acid on EF is dose-dependent and lower doses improve EF while higher ones do not. Clopidogrel improves EF, but more studies in subjects with DM are required. Furthermore, angiotensin- converting-enzyme inhibitors /angiotensin II receptor blockers improve EF. Phosphodiesterase type 5 inhibitors improve endothelial function locally in the corpus cavernosum. Finally, cilostazol exerts favorable effect on EF, nevertheless, more data in people with DM are required.

Keywords: Endothelium, diabetes mellitus, diabetic complications, antidiabetic medication, lipid lower medication, antiplatelet medication, antihypertensive medication.

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Article Details

(E-pub Ahead of Print)
DOI: 10.2174/0929867326666190119154152
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