Interleukin-17A-Related Inflammation Mediates Cardiac Injury in Chronic Relapsing Psoriasis-Like Mouse Model.

Abstract

Psoriasis is an inflammatory disease characterised by chronic recurrent relapses. Previous observational studies have shown that patients with psoriasis are predisposed to cardiovascular comorbidities, but few studies have investigated the impact of psoriasis-related chronic inflammation on cardiac function. In this study, we used imiquimod (IMQ) to establish psoriasis-like mouse models with short-term inflammation (IMQ-ST) or long-term repeated inflammation (IMQ-LT), to mimic acute or chronic recurrent pathophysiology of psoriasis inflammation. The inflammatory pattern in the hearts of IMQ-ST mice and IMQ-LT mice was similar to that in the skin, characterised by increased level of interleukin (IL)-17A and proportion of IL-17A-producing γδT cells. However, only IMQ-LT mice showed declined cardiac function, significant myocardial tissue necrosis, and decreased expression of genes encoding structural and functional proteins in cardiomyocytes. Furthermore, IL-17A neutralisation markedly alleviated myocardial injury and improved cardiac function in IMQ-LT mice. In conclusion, we demonstrated that IL-17A-mediated inflammation was present in the skin and heart of acute and chronic psoriasis-like mouse models. However, only IMQ-LT mice developed myocardial injury and declined cardiac function, which could be prevented by IL-17A neutralisation.