Role of mechanical factors in modulating cardiac fibroblast function and extracellular matrix synthesis.
The cardiac fibroblast is the most abundant cell type present in the myocardium and is mainly responsible for the deposition of extracellular matrix (ECM). Important components of cardiac ECM include structural and adhesive proteins such as collagen and fibronectin. Excess deposition of cardiac ECM (fibrosis) has been associated with the pathophysiological mechanical overload of the heart. Therefore, the role of cardiac fibroblasts in "sensing", "integrating" and "responding" to mechanical stimuli is of great interest. The development of in vitro strain apparatuses has allowed scientists to investigate the effects of mechanical stimuli on cardiac fibroblast function. Cardiac fibroblasts express ECM receptors (integrins) which couple mechanical stimuli to functional responses. Mechanical stimulation of cardiac fibroblasts has been shown to result in activation of various signal transduction pathways. The application of defined mechanical stimuli to cultured cardiac fibroblasts has been associated with ECM gene expression, growth factor production, release and/or bioactivity as well as collagenase activity. Ultimately, for fibrosis to develop the overproduction of ECM must overcome any associated increases in collagenase activity. Mechanically induced upregulation of ECM production may follow direct or indirect pathways through the autocrine or paracrine action of growth factors. Given the complex nature of the interstitial milieu of the working heart, additional research is needed to further our understanding of the roles that mechanical stimuli play in excess deposition of myocardial ECM.
MacKenna
D
D
UCSD Med. Ctr. 8412, Department of Medicine, 200 West Arbor St., San Diego, CA 92103-8412, USA.
Summerour
S R
SR
Villarreal
F J
FJ
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D017364:Collagenases / Q000378:metabolism; D005109:Extracellular Matrix / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology*; D013314:Stress, Mechanical; D016212:Transforming Growth Factor beta / Q000378:metabolism; D020257:Ventricular Remodeling
D016326:Extracellular Matrix Proteins; D016023:Integrins; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D007334:Insulin-Like Growth Factor I; D017364:Collagenases