© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Regulation of cardiovascular collagen synthesis by mechanical load
Cardiovascular Research Group, Centre for Cardiopulmonary Biochemistry and Respiratory Medicine, University College London Medical School, The Rayne Institute, 5 University Street, London, WC1E 6JJ, UK
Jill.Bishop@ucl.ac.uk
* Corresponding author. Tel.: +44-171-209-6972; fax: +44-171-209-6973
Received 22 October 1998; accepted 10 January 1999
KEYWORDS Collagen; Heart; Artery; Mechanical load
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1 Introduction |
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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
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2 Stimulation of cardiovascular matrix remodelling in the heart and vasculature |
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2.1 Vascular remodelling
2.2 Cardiac hypertrophy and fibrosis
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3 Regulation of procollagen gene expression |
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4 Influence of the extracellular matrix on the mechanical loading of cardiovascular cells |
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5 Effect of mechanical load on cardiovascular fibroblast function |
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5.1 Stimulation of cell replication by mechanical load
5.2 Enhancement of procollagen synthesis by mechanical load
5.3 Mechanical stimulation of autocrine and paracrine growth factors
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6 How are mechanical forces perceived by the cells? mechanisms of mechano-signal transduction |
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6.1 Mechano-sensory mechanisms
6.2 Cytoskeletal deformation
6.3 Integrins as mechano-receptors
6.4 Stretch-activated ion channels
6.5 Second messenger pathways
6.6 Tertiary signals: activation of transcription factors
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7 Synergistic interactions between growth factors and mechanical load in the stimulation of cardiovascular cell growth |
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8 Future directions |
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