Cardiac fibroblasts: at the heart of myocardial remodeling.

By K. Porter, N. Turner. Pharmacology and Therapeutics, 2009

1,033 citations recorded by the source corpus.

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.

Subfields: Cardiology and Cardiovascular Medicine, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/9b19090e5090a8dba674a16bb9140ba11e956829

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cardiology and Cardiovascular Medicine

1. H. Ruskoaho
2. Virpi Talman
3. A. Takawale
4. Yibin Wang
5. T. Force
6. Z. Kassiri

In Molecular Biology

1. H. Ruskoaho
2. Virpi Talman
3. Yibin Wang
4. B. Rose
5. T. Force
6. Z. Kassiri

In Oncology

1. A. Takawale
2. Z. Kassiri

Citations in the corpus

• Myocardial remodeling after infarction: the role of myofibroblasts (2010, background): “Mainly differentiated from fibroblasts, these cells express contractile proteins and exhibit migratory, proliferative and secretory properties”
• The myofibroblast matrix: implications for tissue repair and fibrosis (2013, neutral): “A number of recent reviews have considered the nature of myofibroblastprogenitors in different organs [21], including resident fibroblasts [3,19,22-25], fibrocytes[26-28],smooth muscle cells [29], pericytes[30-33], epithelial and endothelial cells undergoing endothelial (EndoMT) or epithelial-to-mes”
• Mitogen-activated protein kinase signaling in the heart: angels versus demons in a heart-breaking tale. (2010, background): “However, given their importance in cardiac pathologies, the reader is directed to a number of excellent reviews regarding these topics (33, 131, 136, 160, 259, 325, 346).”
• Cardiac fibrosis in myocardial infarction—from repair and remodeling to regeneration (2016, background): “…statins have been shown to directly inhibit cardiac fibroblast proliferation and migration, fibroblast-myofibroblast transdifferentiation, and ECM turnover, all of which are expected to confer beneficial effects in the myocardial remodeling process (for a review, see Porter and Turner 2009).”
• Cardiac fibroblasts, fibrosis and extracellular matrix remodeling in heart disease (2012, background): “These molecules include cytokines (TNFα, interleukins and TGFβ), active peptides (angiotensin II, endothelin 1) and growth factors [61], which function in the myocardium in autocrine and/or paracrine fashions.”