Microscopy and Microanalysis

Special Section: Keystone Meeting on Extracellular Matrix

Myofibroblasts in the Infarct Area: Concepts and Challenges

Evangelos P. Daskalopoulosa1, Ben J.A. Janssena1 and W. Matthijs Blankesteijna1 c1

a1 Department of Pharmacology, Cardiovascular Research Institute Maastricht, Maastricht University, 50 Universiteitssingel, 6229ER Maastricht, P.O. Box 616, 6200MD Maastricht, The Netherlands

Abstract

Myofibroblasts are differentiated fibroblasts that hold a key role in wound healing and remodeling following myocardial infarction (MI). A large repertoire of stimuli, such as mechanical stretch, growth factors, cytokines, and vasoactive peptides, induces myofibroblast differentiation. Myofibroblasts are responsible for the production and deposition of collagen, leading to the establishment of a dense extracellular matrix that strengthens the infarcted tissue and minimizes dilatation of the infarct area. In addition, cells contributing to fibrosis act on sites distal from the infarct area and promote collagen deposition in noninfarcted tissue, thus contributing to adverse remodeling and consequently to the development of congestive heart failure (CHF). Current drugs that are used to treat post-MI CHF do influence fibroblasts and myofibroblasts; however, their therapeutic efficacy is far from being regarded as ideal. Novel therapeutic agents targeting (myo)fibroblasts are being developed to successfully prevent the cardiac remodeling of sites remote from the infarct area and therefore hinder the establishment of CHF. The purpose of this review article is to discuss the basic concepts of the myofibroblasts' actions in cardiac wound healing processes, factors that influence them, currently available pharmacological agents, and future challenges in this area.

(Received June 01 2011)

(Accepted August 17 2011)

Correspondence:

c1 Corresponding author. E-mail: wm.blankesteijn@maastrichtuniversity.nl