E-selectin in vascular pathophysiology

Abstract

Selectins are a group of Ca²⁺-dependent, transmembrane type I glycoproteins which attract cell adhesion and migration. E-selectin is exclusively expressed in endothelial cells, and its expression is strongly enhanced upon activation by pro-inflammatory cytokines. The interaction of E-selectin with its ligands on circulating leukocytes captures and slows them down, further facilitating integrin activation, firm adhesion to endothelial cells and transmigration to tissues. Oxidative stress induces endothelial cell injury, leading to aberrant expression of E-selectin. In addition, the elevated level of E-selectin is positively related to high risk of inflammation. Dysregulation of E-selectin has been found in several pathological conditions including acute kidney injury (AKI), pulmonary diseases, hepatic pathology, Venous thromboembolism (VTE). Deletion of the E-selectin gene in mice somewhat ameliorates these complications. In this review, we describe the mechanisms regulating E-selectin expression, the interaction of E-selectin with its ligands, the E-selectin physiological and pathophysiological roles, and the therapeutical potential of targeting E-selectin.

Keywords: E-selectin; inflammation; oxidative stress; therapeutic interventions; vascular diseases.

Figure 1

E-selectin’s basic molecular structure and its ligands. (A) E-selectin is composed of five distinct domains. The lectin-like domain, an epidermal growth factor (EGF)-like domain, and a short consensus repeat (SCR) domain. The lectin-like domain is located at the N-terminal region and is responsible for recognizing and binding specific carbohydrate ligands. The EGF-like domain, positioned in the middle, contributes to the overall structure and stability of E-selectin. The C-terminal SCR domain consists of multiple repeat units that facilitate protein-protein interactions and functions in cell adhesion processes. (B) E-selectin anchored on endothelial cells displays binding interactions with a diverse array of ligands on leucocytes, including PSGL-1, ESL-1, CD44, CD43, β2-integrins, and L-selectin. The combination of PSGL-1 on E-selectin activates Rap1, thereby inducing the activation of β2 integrin.