CCR2+ Macrophages and Pressure-Overload Cardiac Hypertrophy and Failure
The model integrates the findings from the current study with prior work (5,7,9,10). During the early compensated phase of pressure overload, there is myocardial up-regulation of chemokine ligands for CCR2 (CCL2, CCL7, CCL12) and innate immune cell expansion including: CCR2+ macrophages (accompanying Ly6Chi monocytosis), dendritic cells, and resident CCR2− macrophages. The CCR2+ macrophage population contributes importantly to early compensatory hypertrophy, antigen presentation, and CD4+ and CD8+ T-cell activation and expansion in the heart and mediastinal lymph nodes (MLNs). CD4+ T cells, alone or together with CCR2+ macrophages, subsequently engender tissue-injurious responses including pathological hypertrophy, interstitial fibrosis, and left ventricular systolic dysfunction. Schematic representations of the heart, LNs, blood vessel, and monocytes/macrophages were adapted from Servier Medical Art (Creative Commons license).