Immune Function of Endothelial Cells: Evolutionary Aspects, Molecular Biology and Role in Atherogenesis

Abstract

Atherosclerosis is one of the key problems of modern medicine, which is due to the high prevalence of atherosclerotic cardiovascular diseases and their significant share in the structure of morbidity and mortality in many countries. Atherogenesis is a complex chain of events that proceeds over many years in the vascular wall with the participation of various cells. Endothelial cells are key participants in vascular function. They demonstrate involvement in the regulation of vascular hemodynamics, metabolism, and innate immunity, which act as leading links in the pathogenesis of atherosclerosis. These endothelial functions have close connections and deep evolutionary roots, a better understanding of which will improve the prospects of early diagnosis and effective treatment.

Participation of Krüppel-like Factors in Atherogenesis

“…In addition to the fact that endothelial cells play an important role in vascular functions such as vasodilation, blood pressure regulation, and angiogenesis, a growing body of evidence is increasing the understanding that endothelial cells are also involved in immune responses [ 124 , 125 ]. Endothelial cell function also includes the regulation of immune cell migration across the vascular barrier through the production of immune mediators such as cytokines and chemokines.…”

“…Endothelial cells express several classes of molecules, such as selectins and integrins, which are involved in leukocyte adhesion and extravasation from the bloodstream. Endothelial cells may also themselves undergo an inflammatory response with activation of adhesion molecules and secretion of proinflammatory cytokines in response to stimuli such as LPS or other pathogens [ 125 , 126 ]. Endothelial cell activation is accompanied by a change in their metabolism, which is known as cellular immunometabolism.…”

Hyperuricemia and Endothelial Function: Is It a Simple Association or Do Gender Differences Play a Role in This Binomial?

“…The ROS react directly with NO, creating high-affinity bonds that reduce the bioavailability of NO through its degradation and inactivation and increase the formation of peroxynitrite, which is capable of causing DNA damage, cell death, and lipid peroxidation. This process is called eNOS decoupling [ 21 ]. Xanthine oxidase is a protein with an enzymatic function that can be converted into the other form of xanthine oxidoreductase, namely xanthine dehydrogenase (XD).…”

“…Endothelial dysfunction is triggered by reduced endothelial nitric oxide synthase (eNOS) activity and the consequent decrease in the availability of nitric oxide (NO). The enzyme eNOS represents the main source of NO production in endothelial cells, where it plays an important function not only in controlling the integrity of the endothelial barrier but also in modulating leukocyte adhesion, platelet aggregation, and angiogenesis [ 21 , 73 ]. Since females are more protected than males against major cardiovascular events, it has long been assumed that estrogen is able to genetically mediate and regulate the expression of eNOS in endothelial cells [ 47 , 74 ] Furthermore, the activation of the enzyme and the formation of NO can also occur through rapid signaling pathways mediated by other factors present in endothelial cells [ 75 ].…”

The Significance of Low Magnesium Levels in COVID-19 Patients

“…Since it disrupts the homeostasis of endothelial cells, magnesium deficiency, combined with cardiovascular risk factors, is considered a promoter of endothelial dysfunction. The impact of hypomagnesemia on endothelial functions is significant, as it contributes to the triggering of oxidative stress and the stimulation of endothelial cell oxidant production [ 32 , 33 , 34 ]. Contrarily, magnesium suppresses vascular oxidative stress [ 35 ].…”