Role of Interleukin 17 in Inflammation, Atherosclerosis, and Vascular Function in Apolipoprotein E–Deficient Mice

Abstract

Objective Interleukin 17A (IL17A) is involved in many inflammatory processes but its role in atherosclerosis remains controversial. We examined the role of IL17A in mouse and human atherosclerosis. Methods and Results Atherosclerosis was induced in ApoE−/− and IL17A/ApoE−/− mice using high fat feeding, angiotensin II infusion, or partial carotid ligation. In ApoE−/− mice, 3 months of high fat diet induced interferon gamma production by splenic lymphocytes, and this was abrogated in IL17A/ApoE−/− mice. IL17A/ApoE−/− mice had reduced aortic superoxide production, increased aortic nitric oxide levels, decreased aortic leukocyte and dendritic cell infiltration, and reduced weight gain after high fat diet compared to ApoE−/− mice. Despite these favorable effects, IL17A deficiency did not affect aortic plaque burden after high fat diet or angiotensin II infusion. In a partial carotid ligation model, IL17A deficiency did not affect percent stenosis but reduced outward remodeling. In this model, neutralization of the related isoform, IL17F, in IL17A/ApoE−/− mice did not alter atherosclerosis. Finally, there was no correlation between IL17A levels and carotid intima-media thickness in humans. Conclusion IL17 contributes to vascular and systemic inflammation in experimental atherosclerosis but does not alter plaque burden. The changes in plaque composition caused by IL17 might modulate plaque stability.

Induction of Endothelial Nitric Oxide Synthase Expression by IL-17 in Human Vascular Endothelial Cells: Implications for Vascular Remodeling in Transplant Vasculopathy

“…Luminal occlusion was not directly examined (21). Consistent with our findings, Madhur et al (46) showed recently that IL-17 does not affect intimal thickening but supports outward remodeling in a mouse model of atherosclerosis. Finally, an alternative explanation for the negative correlation between IL-17-positive cells and luminal occlusion that we observe could be that IL-17 responses predominate early in allogeneic responses.…”

IL-17A Influences Essential Functions of the Monocyte/Macrophage Lineage and Is Involved in Advanced Murine and Human Atherosclerosis

“…Atherosclerosis and its consequences (i.e., myocardial infarction and stroke) remain the major cause of morbidity and mortality in Western countries. Several studies have investigated the role of IL-17A in the development of atherosclerosis with partially controversial results (7)(8)(9)(10)(11)(24)(25)(26), which are at least partially based on the study design, neutralizing Ab versus bone marrow transfer experiments, on the type of diet, and on the location of the analysis of the atherosclerotic lesion. By contrast, the current study evaluated the role of IL-17A on advanced atherosclerotic lesions and its potential impact as a therapeutic target.…”

The altered expression of inflammation-related microRNAs with microRNA-155 expression correlates with Th17 differentiation in patients with acute coronary syndrome

“…8,9 According to previous studies, Th1 cells induce plaque rupture and the onset of acute coronary syndrome (ACS), and Th17 cells contribute to vascular and systemic inflammation and may modulate plaque stability, whereas Treg cells play the opposite role. 10,11 However, the underlying molecular mechanisms of the imbalance of Th cells in atherosclerosis have not been thoroughly clarified. Recently, miRNAs (such as miR-155 and miR-146a) were determined to be key molecules in modulating the differentiation of Th cells.…”