Endothelial Cell Participation in Inflammatory Reaction

Abstract

Inflammation is an old concept that has started to be considered as an important factor in infection and chronic diseases. The role of leukocytes, the plasmatic components, then of the mediators such as prostaglandins, cytokines, and, in recent decades, of the endothelium has completed the concept of the inflammation process. The function of the endothelium appeared to be crucial as a regulator or the initiator of the inflammatory process. Culture of human endothelial cells and experimental systems made it possible to define the molecular basis of inflammation in vascular diseases, in diabetes mellitus, atherosclerosis, vasculitis and thromboembolic complications. Advanced glycation end product receptor (RAGE), present on endothelial cells (ECs) and monocytes, participates in the activation of these cells in inflammatory conditions. Inflammasome is a cytosolic multiprotein that controls the response to diverse microorganisms. It is positively regulated by stimulator of interferon response CGAMP interactor-1 (STING1). Angiogenesis and thrombotic events are dysregulated during inflammation. ECs appear to be a protector, but also a possible initiator of thrombosis.

Keywords: SARS-CoV-2; angiogenesis; endothelial cells; inflammasome; inflammation; thrombosis.

Figure 1

Cultured Human endothelial cells. Human Umbilical Vein Endothelial Cells (HUVEC) were cultured in Petri dishes until confluence and observed using an inverted microscope (×70) (a). In the ultrastructure the Weibel-Palade bodies (W) (electron microscope, ×50,000) used as a hallmark of endothelial cells, are secretory organelles used for post-synthesis storage in endothelial cells (b).

Figure 2

Inflammation and thrombosis in the vascular endothelium. Platelets adhering to the subendothelium, including von Willebrand factor (VWF) recruiting circulating platelets to form an aggregate. Leukocyte integrins bind to Vascular Cell Adhesion Molecule-1 (VCAM-1) and Intercellular Adhesion Molecule (ICAM). Activation of the receptor RAGE, a multiligand receptor, induces the release of Macrophage Chemoattractant Protein-1 (MCP-1) and Interleukin-6 (IL-6), and the production of Tissue Factor (TF). Monocytes stimulated by bacteria, endotoxins and viruses release tumor necrosis factor (TNF) and interleukin-1 (IL-1).

Figure 3

In vitro capillary tube formation. HUVEC grown on a synthetic matrix formed capillary tubes (11.2 ± 0.9 per mm²) (a). When HUVEC were cocultured with human peritoneal mesothelial cells (HPMC) activated by AGE or cytokines, they released Vascular Endothelial Growth Factor (VEGF), which promotes capillary tube formation (19.7 ± 0.6 per mm²) (b).

Figure 4

Molecular structure of the Receptor for Advanced Glycation End products (RAGE). Structure of full-length RAGE, including three Ig-like domains: the variable (Ig V) domain, two constants (Ig C1 and Ig C2) in the extracellular part, a single transmembrane domain (TM), and one short cytosolic tail (IC).