Early development of myocardial inflammation following myocardial infarction (MI) is essential for healing of the injury. During this phase, necrotic cardiomyocytes (CMs) release pro-inflammatory “damage associated molecular patterns”, or DAMPs. DAMPs trigger innate immune signaling pathways in the myocardium leading to a primary immune response orchestrated by inflammatory phagocytes. It is followed by a resolution and proliferation phase characterized by the activation of fibroblasts and reparative scar formation. Dysregulation in these processes promote alterations in the myocardium and lead to adverse cardiac remodeling. We previously demonstrated that Interleukin-1alpha (IL-1a) is the primary DAMP released by necrotic CMs in vitro and is essential for a full magnitude early inflammatory response in the myocardium in vivo.

Present study aims at defining the role of IL-1a in the process of post-MI inflammation, cardiac remodeling and heart failure by comparing the response to MI of IL-1a-competent (WT), systemic IL-1a knockout (KO) mice and CMs conditional KO (cKO) mice.

Mice underwent permanent ligation of the LAD coronary artery. Inflammatory and fibrotic responses of the myocardium were analyzed by western blotting, ELISA, qPCR and FACS for the phagocytic immune cells content within the myocardium during the first week post-MI. Echographic measurements of cardiac dimensions and function were made 4 to 6 weeks post-MI.

KO mice showed a slight decrease in inflammatory parameters along with decreased ratio of pro-inflammatory macrophages in the first week after MI as compared to WT. We observed a strong decrease in fibrotic markers and TGF-beta responsive genes 7 days post-MI and reduced dimensions of left ventricle 4 to 6 weeks post-MI in KO compared to WT mice, which was not the case in cKO.

IL-1a, from an origin other than CMs, exacerbates post-MI remodeling, making it a presumed therapeutic target.