Expression of IL17A in human atherosclerotic lesions is associated with increased inflammation and plaque vulnerability

Introduction: A chronic (auto)immune response is the critical mechanism in atherosclerosis. Interleukin-17A is a pivotal effector cytokine, which modulates immune cell trafficking and initiates inflammation in (auto)immune and infectious diseases. However, expression of IL-17A in the context of human atherosclerosis has not been studied so far.Methods: Carotid artery plaques were collected from 79 patients undergoing endarterectomy. Patients were grouped according to their symptomatic status (TIA, stroke), plaque morphology and medication. Quantitative RT-PCR was used to analyze tissue inflammation and immunohistochemistry to assess lesion morphology. Results: Carotid plaques from patients with ischemic symptoms were characterized by a highly activated inflammatory milieu including accumulation of T cells (p=0.04) and expression of IL6 and VCAM1 (p=0.02, p=0.01). Expression of IL17A and its positive regulators IL21 and IL23 was present in atherosclerotic lesions, significantly upregulated in atheromas of symptomatic patients (p=0.03, p=0.004, p=0.03) and expression of IL17A and IL21 showed a strong correlation (p=0.002, r=0.52). Vulnerable plaque characteristics such as thrombotic or lipid-rich lesions were significantly associated with IL17A expression levels (p=0.03, p=0.02), but IL17A expression was not associated with decalcification, represented by Osteopontin. In addition, IL17A showed a marked negative correlation with the potent anti-inflammatory/atheroprotective cytokine IL10 (p=0.0006, r=-0.46). Furthermore, treatment with a HMG-CoA reductase inhibitor or acetylsalicylic acid showed reduced levels of IL21 , IL23 and VCAM1 , (all p<0.05), but did not influence IL17A . Conclusion: The association of IL-17A with ischemic symptoms and vulnerable plaque characteristics suggests that the pro-inflammatory cytokine IL-17A may contribute to atherosclerosis und plaque instability.