Regulation of myocardial extracellular matrix components by mechanical and chemical growth factors

The cardiac fibroblast is numerically the most abundant cell in the myocardium and is responsible for the deposition of the extracellular matrix (ECM). The cardiac ECM is a hierarchical, three-dimensional network in the heart, of which fibrillar collagens types I and III are the major structural components. Normal and pathological deposition of fibrillar collagen in the heart appears to rely on the regulation of ECM components such as fibronectin. Many humoral mediators have been noted to modulate the function of cardiac fibroblasts. In particular, angiotensin II and transforming growth factor-β1 have gained recent attention. However, growth factors such as endothelin, ANF, and catecholamines among others are also noted to modify cardiac fibroblast function. Cardiac fibroblasts are also capable of synthesizing and releasing many of the above mentioned growth factors which in an autocrine or paracrine fashion may modulate myocardial cell functions. Cardiac fibroblasts have also been noted to secrete a potent growth factor that stimulates cardiac myocyte hypertrophy. Recent studies using stretch apparatuses on cardiac fibroblasts also indicate that these cells respond to such types of mechanical stimuli. Unfortunately, little is known about human cardiac fibroblasts since most studies have utilized cells isolated from animal species. The following study summarizes our current state of knowledge in the field of mechanical and chemical regulation of myocardial ECM.