Interleukin‐5 alleviates cardiac remodelling via the STAT3 pathway in angiotensin II‐infused mice

Abstract

AbstractInterleukin‐5 (IL‐5) has been reported to be involved in cardiovascular diseases, such as atherosclerosis and cardiac injury. This study aimed to investigate the effects of IL‐5 on cardiac remodelling. Mice were infused with angiotensin II (Ang II), and the expression and source of cardiac IL‐5 were analysed. The results showed that cardiac IL‐5 expression was time‐ and dose‐dependently decreased after Ang II infusion, and was mainly derived from cardiac macrophages. Additionally, IL‐5‐knockout (IL‐5−/−) mice were used to observe the effects of IL‐5 knockout on Ang II‐induced cardiac remodelling. We found knockout of IL‐5 significantly increased the expression of cardiac hypertrophy markers, elevated myocardial cell cross‐sectional areas and worsened cardiac dysfunction in Ang II‐infused mice. IL‐5 deletion also promoted M2 macrophage differentiation and exacerbated cardiac fibrosis. Furthermore, the effects of IL‐5 deletion on cardiac remodelling was detected after the STAT3 pathway was inhibited by S31‐201. The effects of IL‐5 on cardiac remodelling and M2 macrophage differentiation were reversed by S31‐201. Finally, the effects of IL‐5 on macrophage differentiation and macrophage‐related cardiac hypertrophy and fibrosis were analysed in vitro. IL‐5 knockout significantly increased the Ang II‐induced mRNA expression of cardiac hypertrophy markers in myocardial cells that were co‐cultured with macrophages, and this effect was reversed by S31‐201. Similar trends in the mRNA levels of fibrosis markers were observed when cardiac fibroblasts and macrophages were co‐cultured. In conclusions, IL‐5 deficiency promote the differentiation of M2 macrophages by activating the STAT3 pathway, thereby exacerbating cardiac remodelling in Ang II‐infused mice. IL‐5 may be a potential target for the clinical prevention of cardiac remodelling.