Investigating the Role of IL-21/IL-21R axis in Atherosclerosis formation

Abstract

Atherosclerosis is a chronic inflammatory disease in the heart, the disease forms through the accumulation of macrophages which engulfs oxidised LDL (oxLDL), the process then forms what is called a foam cell, this plays multiple roles through the possible stimulation of different immune cells, forming plaques that continuously grow, which then block the flow of the blood stream, potentially causing a heart attack. Interleukin-21 (IL-21) is a type I cytokine which is produced by different types of immune cells, like CD4+ T cells. It signals through the IL-21 Receptor (IL-21R). IL-21R is commonly produced in immune cells like B cells and Natural Killer Cells. The study aimed to investigate the effects of IL-21 signalling in male wild type (WT) C57BL/6J and male IL-21 receptor knockout (IL-21R-/-) mice, which were induced with PCSK9 overexpression and a Western diet. The study focused on the quantification of plaque size, necrotic core size, and Virmani classification using Oil red O (ORO) stain, and collagen content quantification using Picrosirius Red stain. Statistical analysis data were expressed as mean ± standard error of the mean (SEM). Normality test was assessed using the Shapiro-Wilk test. If the test was applicable, we used the Unpaired t-test; if not, we used the Mann-Whitney U test. IL-21R-/- mice showed a significantly smaller plaque area, as well as changes in plaque composition with a higher proportion of intimal xanthoma (IX), and fewer fibrocalcific atheroma (FCA). While the necrotic core percentage was lower in IL-21R-/- mice, it did not reach statistical significance, which suggests a possible trend for more stable plaques. Collagen content was similar between groups and did not reach statistical significance. We concluded that the IL-21/IL-21R axis can affect the plaque size, but it does not affect the fibrotic content of the plaque. This lends to the importance of Interleukins.