IL-27 promotes cardiac fibroblast activation and aggravates cardiac remodeling post myocardial infarction
Xiaoxue Ma,
Qingshu Meng,
Shiyu Gong,
Shanshan Shi,
Xiaoting Liang,
Fang Lin,
Li Gong,
Xuan Liu,
Yinzhen Li,
Mimi Li,
Lu Wei,
Wei Han,
Leng Gao,
Zhongmin Liu,
Xiaohui Zhou
Affiliations
Xiaoxue Ma
Shanghai East Hospital, Jinzhou Medical University, Jinzhou, 121000, China; Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China
Qingshu Meng
Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China; Shanghai Heart Failure Research Center, Shanghai, 200120, China
Shiyu Gong
Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China
Shanshan Shi
Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China; Shanghai Heart Failure Research Center, Shanghai, 200120, China
Xiaoting Liang
Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China
Fang Lin
Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China; Shanghai Heart Failure Research Center, Shanghai, 200120, China
Li Gong
Shanghai East Hospital, Jinzhou Medical University, Jinzhou, 121000, China; Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China
Xuan Liu
Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China; Department of Cardiovascular Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China
Yinzhen Li
Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China
Mimi Li
Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China; Shanghai Heart Failure Research Center, Shanghai, 200120, China
Lu Wei
Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China; Shanghai Heart Failure Research Center, Shanghai, 200120, China
Wei Han
Department of Heart Failure, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China
Leng Gao
Translational Medical Center for Stem Cell Therapy & Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, PR China
Zhongmin Liu
Shanghai Heart Failure Research Center, Shanghai, 200120, China; Department of Cardiovascular Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China; Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai 200120, China; Corresponding author. Research Center for Translational Medicine, Department of Cardiovascular Surgery, Shanghai East Hospital, Tongji University School of Medicine 150 Jimo Rd, Pudong, Shanghai, 200120, China.
Xiaohui Zhou
Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China; Shanghai Heart Failure Research Center, Shanghai, 200120, China; Corresponding author. Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine 150 Jimo Rd, Pudong, Shanghai, 200120, ORCID, China.
Excessive and chronic inflammation post myocardial infarction (MI) causes cardiac fibrosis and progressive ventricular remodeling, which leads to heart failure. We previously found high levels of IL-27 in the heart and serum until day 14 in murine cardiac ischemia‒reperfusion injury models. However, whether IL-27 is involved in chronic inflammation-mediated ventricular remodeling remains unclear. In the present study, we found that MI triggered high IL-27 expression in murine cardiac macrophages. The increased expression of IL-27 in serum is correlated with cardiac dysfunction and aggravated fibrosis after MI. Furthermore, the addition of IL-27 significantly activated the JAK/STAT signaling pathway in cardiac fibroblasts (CFs). Meanwhile, IL-27 treatment promoted the proliferation, migration and extracellular matrix (ECM) production of CFs induced by angiotensin II (Ang II). Collectively, high levels of IL-27 mainly produced by cardiac macrophages post MI contribute to the activation of CFs and aggravate cardiac fibrosis.
