Regulation of cardiovascular collagen synthesis by mechanical load.

Time for primary review 20 days. The cardiovascular system is constantly exposed to mechanical perturbation from shear and tensile stresses. During development cardiovascular cells respond to changes in mechanical load; growing, dividing and laying down extracellular matrix. Changes in the normal levels of these forces then have further profound effects on these cells resulting in abnormal changes in cardiovascular structure and consequently function. These remodelling processes suggest that the mechanical environment is a key modulator of cell function. The importance of mechanical forces in the regulation of tissue growth, development and disease has been appreciated for many years. Early studies in the 1960–70s demonstrated, for example, the importance of mechanical load in skeletal muscle growth and development. It was determined that even in the presence of adequate nutrition, and with hormonal and neuronal control, skeletal muscle would not grow without mechanical stimulation [1–3]. The reverse is also true – disuse of a skeletal muscle leads to atrophy [4]. Similarly bone growth and remodelling is dependent on continuous stimuli of pressure and tension [5]. Growth of the lung is also partly regulated by mechanical forces [6]. The response of the cardiovascular system to mechanical stimuli is therefore not unique, however the ability of the cardiovascular system to respond to changes in physical forces by changing the physical properties of the cardiovascular tissues in an attempt to normalise these forces (see Fig. 1) – makes this reciprocal interaction between structure and function and the mechanical environment an extremely fascinating area of study. Fig. 1 Reciprocal relation between mechanical forces and cardiovascular remodelling The cardiovascular system responds to changes (Δ) in haemodynamics by cell hypertrophy, proliferation and extracellular matrix deposition. This tissue remodelling results in changes in the physical properties of the tissues which may be sufficient to counteract the altered … * Corresponding author. Tel.: +44-171-209-6972; fax: +44-171-209-6973