Collagen turnover and its regulation in the normal and hypertrophying heart

Eighteen different collagen types have now been identified, at least five of which are found in the extracellular matrix of the heart. The interstitial collagens, types I and III are the most abundant components. Due to their tensile strength and arrangement in a network, surrounding and inter-connecting myocytes and capillaries, these collagens transmit forces throughout the myocardium, maintain cardiac structure during the cardiac cycle and contribute to the visco-elastic properties of the myocardium. Early application of isotopic techniques to assess turnover suggested that heart collagen, in contrast to cytoplasmic proteins, was virtually inert. The later development of more accurate methods for measuring its synthesis and degradation rates revealed that collagen turnover was quite rapid and that heart cells synthesize and degrade collagens throughout life. Thus, changes in the balance between synthesis and degradation may lead to changes in the composition of the collagen network, which may have marked effects on compliance, resulting in changes in heart function. Current research is focused on the role of mechanical forces and growth factors in the regulation of collagen metabolism. An understanding of the regulatory mechanisms involved in controlling collagen metabolism is fundamental to the development of agents that may reverse or prevent excess collagen deposition in cardiovascular diseases.