Oxidation and modifi cation of extracellular matrix and its role in disease

There is accumulating evidence that damage to extracellular materials and particularly the extracellular matrix, can play a major role in multiple human pathologies. In contrast to cells, the extracellular compartment of most biological tissues is relatively poorly equipped to prevent or repair damage caused by oxidation due to lower levels of antioxidant defenses (low molecular mass and enzymatic) and repair systems (both catabolic and enzymatic). The extracellular compartment is therefore likely to be subject to both an increased extent of damage and an overall accumulation of damage due to slow turnover and/or poor repair. The nature and consequences of damage to the extracellular matrix is poorly understood, despite evidence that changes in matrix structure infl uences not only structural integrity, but also cell adhesion, proliferation, migration and signaling, and cytokine and growth factor binding. In this article the nature of the extracellular matrix is briefl y reviewed, together with evidence for the presence of matrix modifi cations in cardiovascular disease. The oxidants and mechanisms that are known to damage extracellular matrix are reviewed, together with the limited data available to date on how such changes aff ect structural properties and cellular behavior.