The effect of macrophage inhibitors on the inflammatory response in a mouse model of heart failure 3242

Description Inflammation plays a major role in the development and progression of heart failure, which is proven by multiple studies. M1 macrophages have been found to worsen this inflammatory response. Pharmacological intervention that targets this macrophage subset may prove beneficial. We are testing the anti-inflammatory effect of three macrophage inhibitors. We hypothesize that macrophage inhibitors will restore cardiac structure and stimulate macrophage polarization. To investigate this, myocardial infarction (MI) was induced in 10-week-old C57BL/6J mice by left anterior descending coronary artery ligation. Three groups of mice were treated with one inhibitor for each group 24 hours after MI: 35mg/kg of liposomal clodronate, 40mg/kg of macrophage migration inhibitory factor antagonist (MIF098) and 32mg/kg of semapimod tetrahydrochloride (CNI-1493). Blood samples were collected at 48 hours post MI to quantify multiple proinflammatory and anti-inflammatory cytokines in serum using ELISA. Cardiac tissues were harvested 14 days after MI, processed and stained using Masson trichrome stain and hematoxylin and eosin stain to visualize collagen deposition and cardiac infiltration by macrophages respectively. Cardiac primary cells were extracted to assess macrophage expression and polarization using flow cytometry analysis. Preliminary results show an anti-inflammatory effect of the macrophage inhibitors used, demonstrated by a reduced production of pro-inflammatory cytokines.