Cardiac fibroblast activation during myocardial infarction wound healing

•Cardiac fibroblasts undergo temporal pattern changes throughout the wound healing response.•Resident fibroblasts work to maintain cardiac homeostasis, producing sufficient extracellular matrix (ECM) to coordinate normal turnover.•Myocardial infarction (MI) day 1 fibroblasts are pro-inflammatory, day 3 fibroblasts are proliferative and pro-angiogenic, and day 7 fibroblasts are scar producing and anti-angiogenic.•By MI day 28, fibroblasts have established a neohomeostasis, de-activating while continuing to produce sufficient ECM to coordinate the new kinetics of turnover. Cardiac wound healing after myocardial infarction (MI) evolves from pro-inflammatory to anti-inflammatory to reparative responses, and the cardiac fibroblast is a central player during the entire transition. The fibroblast mirrors changes seen in the left ventricle infarct by undergoing a continuum of polarization phenotypes that follow pro-inflammatory, anti-inflammatory, and pro-scar producing profiles. The development of each phenotype transition is contingent upon the MI environment into which the fibroblast enters. In this mini-review, we summarize our current knowledge regarding cardiac fibroblast activation during MI and highlight key areas where gaps remain.