Cardiac fibroblast activation during myocardial infarction wound healing: Fibroblast polarization after MI

Abstract

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.

Keywords: fibroblast; inflammation; myocardial infarction; scar formation; wound healing.

Figure 1.. Cardiac fibroblast activation along the time continuum of response to myocardial infarction (MI).

Before MI, fibroblasts are homeostatic and producing extracellular matrix (ECM) to allow normal physiology. At MI day 1, fibroblasts convert to a pro-inflammatory phenotype, signaling activation of inflammatory signaling. At MI day 3, fibroblasts polarize to a proliferative and pro-angiogenesis profile. Peak expression in the genes listed correspond to adaptations in cell and left ventricle physiology (function). At MI day 7, fibroblasts promote ECM synthesis to form the infarct scar and inhibit angiogenic signaling. At MI day 28, fibroblasts return to a state of neo-homeostasis, once again supporting the normal turnover of ECM to support the new infarct environment. Updated from [4].