INTERACTIONS BETWEEN CELLS AND EXTRACELLU LAR-MATRIX AND ELASTIC PROPERTIES OF LARGE ARTERY WALL

The effects of increased large arteries stiffness are an elevation of pulse pressure and the development of left ventricular hypertrophy, bo th considered as cardiovascular risk factors independent of mean arter ial pressure. The mechanical properties of the arterial wall depends n ot only on the smooth muscle cells, elastin and collagen contents but also on the way these components are spatially organized within the me dia, a process which may he regulated by extracellular matrix adhesion proteins and their cell surface integrin receptors. Interactions betw een vascular smooth muscle cell (VSM) and the extracellular matrix (EC M) play an important role on cell differentiation and signal transduct ion pathways induced by the ECM components. Mechanisms that link cytos keletal and signalling molecules to integrins have been recently subje ct of intensive investigation. From a mechanical point of view, a cent ral role could be attributed to the dense plaque which belongs to the cell-matrix adherent junctions. Dense plaques are composed of associat ed cytoskeletal proteins, vinculin, talin, paxilin and tensin linked t o ECM proteins via integrin receptors. Molecular interactions in dense plaque are regulated by aggregation, conformational changes, phosphor ylation and mechanical forces. Expression of integrins in normal and p athological vessels are relatively unexplored. In human hypertension, the hypertrophy of the arterial wall is accomplished without change in its intrinsic elastic properties assessed by the incremental elastic modulus. Aortic fibronectin expression is increased in spontaneously h ypertensive rats (SHR). By increasing the cell-matrix attachments, fib ronectin may contribute to protect the arterial wall components of SHR s against mechanical deterioration, for instance rupture of elastin fi bers, through an increase in the maximum acceptable circumferential wa ll stress. In atherosclerotic vessels, matrix production might be seen in the earlier stages of atherosclerotic plaque formation, whereas th e converse might be true of the latter stages when adhesion is vital i n the prevention of plaque rupture. The integrin role is underestimate d nevertheless it can play an important function in the stability of t he plaque. Further studies using confocal microscopy, and specific ant i-integrin monoclonal antibodies are needed to determine their precise role in the mechanical properties of large arteries. If we can better understand the role of integrins activation and conformational modifi cations with other adhesion molecules, it Mill be possible to modulate their function and thus intervene at the very basis of human vascular disease.