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

doi:10.1016/j.heliyon.2023.e17099

IL-27 promotes cardiac fibroblast activation and aggravates cardiac remodeling post myocardial infarction

Heliyon. 2023 Jun 18;9(6):e17099. doi: 10.1016/j.heliyon.2023.e17099. eCollection 2023 Jun.

Authors

Xiaoxue Ma^{1

2}, Qingshu Meng^{2

3}, Shiyu Gong⁴, Shanshan Shi^{2

3}, Xiaoting Liang², Fang Lin^{2

3}, Li Gong^{1

2}, Xuan Liu^{2

5}, Yinzhen Li², Mimi Li^{2

3}, Lu Wei^{2

3}, Wei Han⁶, Leng Gao⁷, Zhongmin Liu^{3

5

8}, Xiaohui Zhou^{2

3}

Affiliations

¹ Shanghai East Hospital, Jinzhou Medical University, Jinzhou, 121000, China.
² Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
³ Shanghai Heart Failure Research Center, Shanghai, 200120, China.
⁴ Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
⁵ Department of Cardiovascular Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
⁶ Department of Heart Failure, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
⁷ Translational Medical Center for Stem Cell Therapy & Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, PR China.
⁸ Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai 200120, China.

Abstract

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.

Keywords: Fibroblast; IL-27; Inflammation; Myocardial infarction; Ventricular remodeling.