Figure 2: The spatiotemporal dynamics of chemokine actions in cardiac repair and post-infarction heart failure.

A. Following myocardial infarction, release of damage-associated molecular patterns (DAMPs) by dying cardiomyocytes and degraded extracellular matrix rapidly stimulates marked upregulation of pro-inflammatory CC and CXC chemokines in the infarct zone. As macrophages (Ma) clear the infarct from dead cells and matrix debris, the chemokine response is suppressed. However, in large infarcts, the profound hemodynamic perturbations caused by massive loss of contractile cardiomyocytes causes a low-grade chronic upregulation of pro-inflammatory chemokines in the non-infarcted myocardium. B. In the infarct, early induction of chemokines recruits pro-inflammatory leukocytes, resulting in expansion of phagocytic macrophages and fibroblast activation. The early chemokine response is important for reparative fibrosis. C. In the chronic remodeling phase, high intraventricular pressures increase wall stress and trigger neurohumoral activation, promoting low-level chemokine induction, followed by recruitment and activation of fibrogenic monocytes and macrophages that may cause interstitial fibrosis, contributing to the pathogenesis of adverse remodeling and post-infarction heart failure. EC, endothelial cell; Ly, lymphocyte.