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Pharmacol Ther. 2009 Aug;123(2):255-78. doi: 10.1016/j.pharmthera.2009.05.002. Epub 2009 May 19.

Cardiac fibroblasts: at the heart of myocardial remodeling.

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1
Multidisciplinary Cardiovascular Research Centre (MCRC), Division of Cardiovascular and Neuronal Remodelling, Leeds Institute of Genetics, Health and Therapeutics (LIGHT), University of Leeds, Leeds LS29JT, UK. k.e.porter@leeds.ac.uk

Abstract

Cardiac fibroblasts are the most prevalent cell type in the heart and play a key role in regulating normal myocardial function and in the adverse myocardial remodeling that occurs with hypertension, myocardial infarction and heart failure. Many of the functional effects of cardiac fibroblasts are mediated through differentiation to a myofibroblast phenotype that expresses contractile proteins and exhibits increased migratory, proliferative and secretory properties. Cardiac myofibroblasts respond to proinflammatory cytokines (e.g. TNFalpha, IL-1, IL-6, TGF-beta), vasoactive peptides (e.g. angiotensin II, endothelin-1, natriuretic peptides) and hormones (e.g. noradrenaline), the levels of which are increased in the remodeling heart. Their function is also modulated by mechanical stretch and changes in oxygen availability (e.g. ischaemia-reperfusion). Myofibroblast responses to such stimuli include changes in cell proliferation, cell migration, extracellular matrix metabolism and secretion of various bioactive molecules including cytokines, vasoactive peptides and growth factors. Several classes of commonly prescribed therapeutic agents for cardiovascular disease also exert pleiotropic effects on cardiac fibroblasts that may explain some of their beneficial outcomes on the remodeling heart. These include drugs for reducing hypertension (ACE inhibitors, angiotensin receptor blockers, beta-blockers), cholesterol levels (statins, fibrates) and insulin resistance (thiazolidinediones). In this review, we provide insight into the properties of cardiac fibroblasts that underscores their importance in the remodeling heart, including their origin, electrophysiological properties, role in matrix metabolism, functional responses to environmental stimuli and ability to secrete bioactive molecules. We also review the evidence suggesting that certain cardiovascular drugs can reduce myocardial remodeling specifically via modulatory effects on cardiac fibroblasts.

[Indexed for MEDLINE]

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