IL-17A may be responsible for the pathogenesis of atherosclerosis by inducing the adhesion of leukocytes to vascular endothelium and foam cell formation.
The level of IL-17 and IL-18 in the atherosclerosis and disease control groups was higher than that in the healthy control group, and the level of IL-17 and IL-18 in the atherosclerosis was higher than that in the disease control group.
Fixed effect analysis of the WMD (95% CI) of the changes in gene expression showed that gene expression of the inflammatory (IL-17, IFN-γ and T-bet) and anti-inflammatory (TGF-β and FOXP3) cytokines significantly decreased and increased due to vitamin A supplementation in patients with autoimmune (Multiple sclerosis and atherosclerosis) diseases.
IL-17A appears to be a differential regulator of atherosclerosis and its effects in mouse models suggest that its modulation may have contradictory effects on plaque size and possibly stability in different patient populations.
These data demonstrate that loss of IL-23R does not affect development of experimental atherosclerosis in LDLr-deficient mice, despite a role for IL-23 in differentiation of IL-17-producing T cells.
Due to its pleiotropic character, IL-17A is involved in the development of atherosclerosis, hypertension, diabetic nephropathy, ischaemia-reperfusion injury, fibrosis, glomerulonephritis, nephrotic syndrome, minimal change disease and acute renal allograft rejection.
Based on the studies performed so far, it is assumed that IL-17 contributes to development of atherosclerosis by means of: stimulation of production of proinflammatory compounds; induction of apoptosis of endothelial cells and heart muscle cells; stimulation of von Willebrand factor production; and induction of the matrix metalloproteinase-9 (atherosclerotic plaque rupture).
These findings suggest that the activation of macrophages differentiated with IL-17 by oxLDL contributes to the inflammatory process of atherosclerosis.
Additionally, cytokines such as TNF-α, IL-17A, and other immune pathways are the common links between the pathogenesis of psoriasis and atherosclerosis, and hence the approved treatments for psoriasis, which include selective cytokine inhibition (e.g., anti-TNF, anti-IL-17A, and anti-IL-12/23) and immune modulation (e.g., methotrexate or cyclosporine), provide an opportunity to examine the effect of modulating these pathways on atherogenesis.
Evolving mouse models and clinical trials targeting IL-17-associated pathways continue to elucidate contributions of neutrophils in both atherosclerosis and psoriasis.
We investigated the frequencies of IL-17 and IFN-γ producing CD4+ T-cell subsets in the peripheral blood mononuclear cells (PBMCs) of 10 patients with atherosclerosis and 6 individuals with normal/insignificant coronary artery disease.
Ethnic-specific IL17 gene polymorphism may explain the conflicting results both on the roles of IL17 and Th17 cells in atherosclerosis development and about the epidemiology of CVD in MS population across countries.
Besides this foamy phenotype, IL-17A induced a mixed macrophage-DC phenotype and expression of the nuclear receptor NR1H3/liver X receptor-α, previously identified in the context of atherosclerosis as the master regulator of cholesterol homeostasis in macrophages.
These results show that IL-17 cytokines are induced by high glucose via key signaling pathways leading to lymphocyte activation and relevant to the pathogenesis of diabetic complications like atherosclerosis.
In the current review, we describe recent progress on regulation and signaling of IL-17A, and highlight its impacts on lipid metabolism and atherosclerosis.
Consistent with these observations, we found that peritoneal macrophages from apolipoprotein E-deficient (ApoE-/-) mice fed a high-fat diet (a mouse model of atherosclerosis) exhibited increased xanthine oxidase and NADPH oxidase activities; ROS production; phosphorylation of Syk, Pyk2, MAPK, and CREB; and IL-17A production compared to those from similarly fed ApoE-/-:12/15-LO-/- mice.
Interfering with PAF may offer the opportunity to develop novel therapeutic strategies for inflammatory psoriasis and associated comorbidities, including metabolic syndrome and atherosclerosis, in which the IL-17 axis may be involved.