Hu Mengyan, Cao Han, Zhang Shimin, Zhang Li, Chen Lihong, Xia Yuhan, Zhang Jiayi, Yang Qi, Xue Feng, Li Xia, Zheng Jie
Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China.
Exp Dermatol. 2025 Jul;34(7):e70139. doi: 10.1111/exd.70139.
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.
银屑病是一种以慢性复发性发作为特征的炎症性疾病。既往观察性研究表明,银屑病患者易患心血管合并症,但很少有研究调查银屑病相关的慢性炎症对心脏功能的影响。在本研究中,我们使用咪喹莫特(IMQ)建立具有短期炎症(IMQ-ST)或长期反复炎症(IMQ-LT)的银屑病样小鼠模型,以模拟银屑病炎症的急性或慢性复发病理生理学。IMQ-ST小鼠和IMQ-LT小鼠心脏中的炎症模式与皮肤相似,其特征是白细胞介素(IL)-17A水平升高以及产生IL-17A的γδT细胞比例增加。然而,只有IMQ-LT小鼠表现出心脏功能下降、明显的心肌组织坏死以及心肌细胞中编码结构和功能蛋白的基因表达降低。此外,IL-17A中和显著减轻了IMQ-LT小鼠的心肌损伤并改善了心脏功能。总之,我们证明了IL-17A介导的炎症存在于急性和慢性银屑病样小鼠模型的皮肤和心脏中。然而,只有IMQ-LT小鼠出现心肌损伤和心脏功能下降,而IL-17A中和可以预防这种情况。