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

Excessively chronic inflammation and cardiac fibrosis post myocardial infarction(MI) cause progressive ventricular remodeling, which finally leads to heart failure. We previously found a high level of IL-27 in the heart and serum till day 14 post ischemia-reperfusion heart. However, whether IL-27 is involved in chronic inflammation-mediated ventricular remodeling remains unclear. In the present study, we found IL-27 expression levels in serum and damaged heart tissue were elevated and continued to day14 in mice after myocardial infarction. We also found MI triggered high IL-27 expression in cardiac macrophages. The increased expression of IL-27 in the serum is correlated with cardiac dysfunction and fibrosis after MI in mice. Furthermore, addition of IL-27 significantly activated the JAK/STAT signaling pathway in cardiac fibroblasts (CFs). Meanwhile, treatment with IL-27 promoted the proliferation and migration, as well as the differentiation of CFs to myofibroblasts and ECM production induced by angiotensin II (Ang II). Collectively, high level of IL-27 mainly produced by cardiac macrophages post MI promotes the collagen production of CFs and aggravates cardiac fibrosis.