Role of Hyperlipidemia in the Development of Endothelial Dysfunction

Abstract

The production of powerful vasoconstrictors (endoperoxides, endothelins) and cytokines such as tumor necrosis factor alpha (TNF-α) that suppress nitric oxide (NO) synthesis play a key role in the development of endothelial dysfunction, which leads to disruption of vasorelaxation processes. To date, sufficient data have been accumulated showing that the development of endothelial dysfunction, caused, in particular, by quantitative and qualitative disruption of lipid homeostasis, is of paramount importance in the progression of systemic vascular pathology. The effect of oxidized low-density lipoproteins (oxy-LDL) on the vascular wall initiates the development of endothelial insufficiency and the formation of an atherosclerotic plaque. Oxy-LDL also mediates vasoconstriction of coronary vessels by reducing eNOS, inhibiting NO and increasing endothelin production. The development of hyperlipidemia initiates a proliferative response of endothelial cells with subsequent changes in their functional activity and expression of proteins of the “proinflammatory endothelial phenotype” that play an important role in regulating the local inflammatory process. At the same time, hyperexpression of cell adhesion molecules VCAM-1, ICAM-1 and E-selectin is a decisive step in increasing the adhesive activity of monocytes and their migration into the vascular wall. An important link in the formation of endothelial dysfunction in hyperlipidemia, according to many authors, is a change in the amount and activity of endothelial nitric oxide synthase (eNOS) and, as a consequence, a violation of NO production by the endothelium.