Chistiakov DA, Orekhov AN, Bobryshev YV.
Exp Mol Pathol. 2016 Sep 9;101(2):231-240. doi: 10.1016/j.yexmp.2016.09.002. [Epub ahead of print]
The relative resistance of fibroblasts to hypoxia and their remarkable adaptive plasticity in response to rapid changes in local tissue microenvironment made interstitial cardiac fibroblasts to be a key player in post-myocardial infarction myocardial repair. Cardiac fibroblasts are abundantly presented in the interstitial and perivascular extracellular matrix. These cells can be rapidly mobilized in response to cardiac injury. Inflammatory activation of fibroblasts leads to the loss of their quiescent phenotype and inhibition of matrix-producing capacity. Acute inflammation that follows the infarct induces production of inflammatory mediators, matrix-degrading activity, proliferation, and migration of fibroblasts. Fibroblasts migrate to the injured myocardial site where undergo transdifferentiation to myofibroblasts in response to anti-inflammatory and mitogenic stimuli. They acquire capacity to synthesize matrix and contractile proteins. In the infarcted zone, fibroblasts/myofibroblasts actively proliferate, expand, and extensively produce and deposit collagen and other matrix proteins. The proliferative stage of heart healing transits to the scar maturation stage, in which collagen-based scar exhibits formation of intramolecular and extramolecular cross-links, deactivation and apoptosis of fibroblasts/myofibroblasts. Generally, cardiac reparation is strongly controlled. Inability to pass from one repair stage to another in a timely manner can induce detrimental events such as expansion of the infarct area due to advanced inflammation, cardiac fibrosis and adverse remodeling due to the excessive proliferative and profibrotic response, left ventricular hypertrophy, arrhythmogenicity, and heart failure.
Copyright © 2016 Elsevier Inc. All rights reserved.
Cardiac repair; Fibroblast; Inflammation; Matrix deposition; Myofibroblast; Phenotype plasticity; Scar formation