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.