Title:The Two Faces of Interleukin-17A in Atherosclerosis
Volume: 18
Issue: 7
Author(s): Mohammadreza Akhavanpoor, Hamidreza Akhavanpoor, Christian A. Gleissner, Susanne Wangler, Andreas O. Doesch, Hugo A. Katus and Christian Erbel*
Affiliation:
- Department of Cardiology, Angiology and Pneumology, Medical Clinic III, University Hospital Heidelberg, INF 410, 69120 Heidelberg,Germany
Keywords:
Interleukin-17A, pro-atherogenic, anti-atherogenic, plaque vulnerability, atherosclerosis, inflammation.
Abstract: A complex network of different cytokines and chemokines modulates atherosclerosis, a
chronic inflammatory disease. Interleukin-17A (IL-17A) is expressed by different leukocyte subsets
such as CD4+IL-17+ T cells (Th17), γδ T cells, natural killer cells, natural killer T cells, and neutrophils.
IL-17A plays an important role in host defense and is involved in the pathology of different
autoimmune and inflammatory diseases. Recent studies demonstrate an association of IL-17A with
atherosclerosis. IL-17A seems to have primarily pro-inflammatory effects in atherogenesis, although
there are partially controversial results in the literature. In the murine system, several studies indicate
a pro-atherogenic role of IL-17A mediated by increased migration of leukocytes (especially macrophages)
into atherosclerotic lesions, increased expression of pro-inflammatory cytokines and
chemokines as well as plaque destabilizing matrix-metalloproteinases using Apoe-/-
and LDLr-/-
mice.
In contrast, three studies show atheroprotective effects of IL-17A mediated by downregulation of aortic
VCAM-1 expression on endothelial cells and increased collagen production by vascular smooth
muscle cells (VSMCs) in LDLr-/-
mice. In humans, expression of IL-17A was associated with increased
inflammation and plaque vulnerability in human atherosclerotic lesions. Moreover, IL-17A
induced a pro-inflammatory, pro-thrombotic, plaque-destabilizing, and cell-attracting response of the
inflammatory milieu of human plaque tissue samples. Notably, a recently published study challenged
these findings by showing a worse outcome of patients with acute myocardial infarction with low serum
levels of IL-17A. In the following review, we will focus on the recent progress of functional studies
of IL-17A in atherosclerosis and will try to collect explanations for the controversial data.
