Endothelial Cell Metabolism in Vascular Functions

Abstract

The endothelium is the innermost layer of all blood and lymphatic vessels composed of a monolayer of specialized endothelial cells (ECs). It is regarded as a dynamic and multifunctional endocrine organ that takes part in essential processes, such as the control of blood fluidity, the modulation of vascular tone, the regulation of immune response and leukocyte trafficking into perivascular tissues, and angiogenesis. The inability of ECs to perform their normal biological functions, known as endothelial dysfunction, is multi-factorial; for instance, it implicates the failure of ECs to support the normal antithrombotic and anti-inflammatory status, resulting in the onset of unfavorable cardiovascular conditions such as atherosclerosis, coronary artery disease, hypertension, heart problems, and other vascular pathologies. Notably, it is emerging that the ability of ECs to adapt their metabolic status to persistent changes of the tissue microenvironment could be vital for the maintenance of vascular functions and to prevent adverse vascular events. The main purpose of the present article is to shed light on the unique metabolic plasticity of ECs as a prospective therapeutic target; this may lead to the development of novel strategies for cardiovascular diseases and cancer.

Keywords: COVID-19; angiogenesis; caveolin; endothelial cells; endothelial dysfunction; metabolism; vascular disease; vasculogenesis.

Figure 1

Main processes involved in endothelial functions and dysfucntions.

Figure 2

Main steps in vessel sprouting. In poorly perfused tissues ECs exposed to high VEGF concentration extend numerous filopodia and become tip cells, initiating sprouting angiogenesis. Degradation of BM and detachment of mural cells allow the stalk cells behind the tip cells to proliferate, contributing to elongating the nascent sprout. Finally, adjacent sprouts fuse and form the lumen. The new blood vessel is eventually stabilized by the recruitment of mural pericytes and deposition of BM (basement membrane).

Figure 3

Metabolic pathways. Metabolism refers to the sum of all the chemical reactions in the body. Catabolism involves breaking down complex compounds into simpler ones, resulting in the release of chemical energy. Anabolism involves building larger and more complex chemical macromolecules from smaller subunits and requires energy obtained from ATP molecules.