Regenerative Crosstalk between Cardiac Cells and Macrophages

Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00056.2021. Online ahead of print.ABSTRACTAside from the first week postnatal, murine heart regeneration is restricted and responses to damage follow classic fibrotic remodeling. Recent transcriptomic analyses have suggested that significant crosstalk with the sterile immune response could maintain a more embryonic-like signaling network that promotes acute, transient responses. However with age, this response-likely mediated by neonatal yolk sac macrophages-then transitions to classical macrophage-mediated, cardiac fibroblast (CF)-based remodeling of the extracellular matrix (ECM) after myocardial infarction (MI). The molecular mechanisms that govern the change with age and drive fibrosis via inflammation are poorly understood. Using multiple RNA-seq datasets, we attempt to resolve the relative contributions of CFs and macrophages in the bulk healing response of regenerative (postnatal day 1) and non-regenerative hearts (postnatal day 8+). We performed an analysis of bulk RNA-seq datasets from myocardium and cardiac fibroblasts as well as a single-cell RNA-seq dataset from cardiac macrophages. MI-specific pathway differences revealed that non-regenerative hearts generated more ECM and had larger matricellular responses correlating with inflammation, produced greater chemotactic gradients to recruit macrophages, and expressed receptors for danger-associated molecular patterns at higher levels than neonates. T...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Source Type: research