Targeting CXCR1 and CXCR2 receptors in cardiovascular diseases

CXCR1 and CXCR2 chemokine receptors, mainly activated by interleukin 8 (IL-8 or CXCL8), are expressed in a va-riety of cells including, leukocytes, fibroblasts, endothelial cells, and smooth muscle cells. Numerous intracellular mediators are activated by these G protein-coupled receptors based on several factors, including the nature of the ligand, its concentration, and the binding sites with the receptor, levels of the receptor, cell type, and stimulatory environment. Much focus is currently being directed towards CXCR1/2 inhibitors, as these receptors primarily in-duce the chemotaxis of leukocytes, especially neutrophils, during inflammation, a key process in cardiovascular disease (CVD) progression. CXCR1/2 inhibitors show beneficial effects in various animal models of CVD. These ef-fects include reducing the atherosclerotic plaque area, improving the serum lipid profile, attenuation of the dam-age following ischemia-reperfusion, the regulation of blood pressure, and the restriction of cardiac remodeling. Based on these encouraging results, testing CXCR1/2 inhibitors in clinical trials could be of a great importance to limit the inflammatory complications associated with CVDs.(c) 2022 Elsevier Inc. All rights reserved.

Automated summary

CXCR1 and CXCR2 chemokine receptors are critical in inflammation, and CXCR1/2 inhibitors show beneficial effects in preventing cardiovascular disease progression.