The role of cardiac fibroblasts in the transition from inflammation to fibrosis following myocardial infarction

• Published in: Vascular pharmacology Vol. 58; no. 3; pp. 182 - 188
• Main Authors: van Nieuwenhoven, Frans A, Turner, Neil A
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2013
• Subjects: Animals; Cardiac fibroblasts; Cardiovascular; Chemokines - metabolism; Cytokines - metabolism; Fibroblasts - metabolism; Fibrosis; Fibrosis - pathology; Heart; Humans; Inflammation; Inflammation - pathology; Intercellular Signaling Peptides and Proteins - metabolism; Myocardial Infarction - physiopathology; Myocardial remodeling; Myocardium - metabolism; Myocardium - pathology; Myofibroblasts - metabolism; Neovascularization, Physiologic; Ventricular Remodeling; Heart; Cardiac fibroblasts; Inflammation; Myocardial remodeling; Fibrosis
• ISSN: 1537-1891; 1879-3649
• DOI: 10.1016/j.vph.2012.07.003

Abstract Cardiac fibroblasts (CF) play a pivotal role in the repair and remodeling of the heart that occur following myocardial infarction (MI). The transition through the inflammatory, granulation and maturation phases of infarct healing is driven by cellular responses to local levels of cytokines, chemokines and growth factors that fluctuate in a temporal and spatial manner. In the acute inflammatory phase early after MI, CF contribute to the inflammatory milieu through increased secretion of proinflammatory cytokines and chemokines, and they promote extracellular matrix (ECM) degradation by increasing matrix metalloproteinase (MMP) expression and activity. In the granulation phase, CF migrate into the infarct zone, proliferate and produce MMPs and pro-angiogenic molecules to facilitate revascularization. Fibroblasts also undergo a phenotypic change to become myofibroblasts. In the maturation phase, inflammation is reduced by anti-inflammatory cytokines, and increased levels of profibrotic stimuli induce myofibroblasts to synthesize new ECM to form a scar. The scar is contracted through the mechanical force generated by myofibroblasts, preventing cardiac dilation. In this review we discuss the transition from myocardial inflammation to fibrosis with particular focus on how CF respond to alterations in proinflammatory and profibrotic signals. By furthering our understanding of these events, it is hoped that new therapeutic interventions will be developed that selectively reduce adverse myocardial remodeling post-MI, while sparing essential repair mechanisms.