Cardiac fibroblasts (CFs) are the major non-contractile cells present in the myocardium, and are primary regulators of synthesis and secretion of extracellular matrix (ECM) proteins. Both proliferation and differentiation of CFs can potentially result in excess ECM protein production and cardiac fibrosis, a condition characterized by a stiffening of the myocardium. This condition is common after myocardial infarction and develops during heart failure, resulting in compromised cardiac function. Hormonal input, as well as input from the surrounding ECM can affect CF proliferation and/or differentiation, and an increase in either one of these parameters will result in elevated ECM production. Consequently, limiting prolonged fibroblast activation and the subsequent detrimental ECM production after myocardial infarction or heart failure might help to preserve left ventricular function.
The specific ECM composition in the myocardium likely imparts significant effects on CF function. However, to date little is known about the effect of the ECM on CF function or the signaling pathways utilized by ECM molecules. In the adult, the myocardium is primarily composed of types I and III collagen, in addition to lower levels of types IV, V, and VI collagen. Extensive remodeling of the ECM occurs following myocardial infarction, and the resulting ECM composition can influence cardiac fibroblast activation in addition to affecting cardiac performance.
My goals are to determine the mechanism of Gq/Gs cross-talk and the functional consequences in CFs, to determine the functional effects of specific types of collagen on CF differentiation and proliferation, and to identify the collagen composition and myofibroblast content post-myocardial infarction.
|School:||Kent State University|
|School Location:||United States -- Ohio|
|Source:||DAI-B 79/08(E), Dissertation Abstracts International|
|Keywords:||Cardiac fibroblasts, Collagen vi, Extracellular matrix, Myofibroblasts, Post-myocardial infarction remodeling|
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