Liposomal clodronate attenuates inflammation in a mouse model of myocardial infarction

Heart failure (HF) is defined as the inability of the heart to pump eough blood to meet the demands of the body. HF affects over 64 million people worldwide and is the leading cause of death, yet current treatment options  do not effectively decrease mortality. The relationship between HF onset and the immune system has been vastly explored, revealing that cardiac tissue undergoes harmful remodeling after a myocardial infarction (MI) that leaves a permanent scar on the heart. Prolonged inflammation and excessive macrophage infiltration lead to a larger infarct area and increased scar formation. Our lab has demonstrated that early inflammation inhibition reduces the damage caused by an (MI). Specifically, we used liposomal clodronate as a macrophage inhibitor to reduce the inflammatory response. In this study, MI was induced using a single high dose of isoproterenol and treated with liposomal clodronate 24hrs after MI. Inflammation levels were assessed through quantification of various pro- and anti-inflammatory cytokines by ELISA and macrophage depletion and polarization was tracked using flow cytometry. At 10 days, heart tissue was harvested for immunohistochemical (IHC) analysis. Our data indicated that liposomal clodronate has anti-inflammatory properties as supported by the decrease in pro-inflammatory cytokines and macrophages. Moreover, IHC analysis revealed less collagen fibers, suggesting a lower area of cardiac remodeling and retained overall structure.