New Approaches to Target Inflammation in Heart Failure: Harnessing Insights from Studies of Immune Cell Diversity

Despite mounting evidence implicating inflammation in cardiovascular diseases, attempts at clinical translation have shown mixed results. Recent preclinical studies have reenergized this field and provided new insights into how to favorably modulate cardiac macrophage function in the context of acute myocardial injury and chronic disease. In this review, we discuss the origins and roles of cardiac macrophage populations in the steady-state and diseased heart, focusing on the human heart and mouse models of ischemia, hypertensive heart disease, and aortic stenosis. Specific attention is given to delineating the roles of tissue-resident and recruited monocyte-derived macrophage subsets. We also highlight emerging concepts of monocyte plasticity and heterogeneity among monocyte-derived macrophages, describe possible mechanisms by which infiltrating monocytes acquire unique macrophage fates, and discuss the putative impact of these populations on cardiac remodeling. Finally, we discuss strategies to target inflammatory macrophage populations.