TY - JOUR

T1 - Mechanisms and consequences of oxidative damage to extracellular matrix

AU - Kennett, Eleanor C

AU - Chuang, Christine Y

AU - Degendorfer, Georg

AU - Whitelock, John M

AU - Davies, Michael Jonathan

PY - 2011/10

Y1 - 2011/10

N2 - Considerable evidence exists for oxidative damage to extracellular materials during multiple human pathologies. Unlike cells, the extracellular compartment of most biological tissues is less well protected against oxidation than intracellular sites in terms of the presence of both antioxidants (low molecular mass and enzymatic) and repair enzymes. The extracellular compartment may therefore be subject to greater oxidative stress, marked alterations in redox balance and an accumulation of damage due to slow turnover and/or poor repair. The nature and consequences of damage to ECM (extracellular matrix) are poorly understood, despite the growing realization that changes in matrix structure not only have structural consequences, but also play a key role in the regulation of cellular adhesion, proliferation, migration and cell signalling. The ECM also plays a key role in cytokine and growth factor binding, and matrix modifications would therefore be expected to alter these parameters. In the present study, we review mechanisms of oxidative damage to ECM, resulting changes in matrix structure and how this affects cellular behaviour. The role of such damage in the development and progression of inflammatory diseases is also discussed with particular reference to cardiovascular disease.

AB - Considerable evidence exists for oxidative damage to extracellular materials during multiple human pathologies. Unlike cells, the extracellular compartment of most biological tissues is less well protected against oxidation than intracellular sites in terms of the presence of both antioxidants (low molecular mass and enzymatic) and repair enzymes. The extracellular compartment may therefore be subject to greater oxidative stress, marked alterations in redox balance and an accumulation of damage due to slow turnover and/or poor repair. The nature and consequences of damage to ECM (extracellular matrix) are poorly understood, despite the growing realization that changes in matrix structure not only have structural consequences, but also play a key role in the regulation of cellular adhesion, proliferation, migration and cell signalling. The ECM also plays a key role in cytokine and growth factor binding, and matrix modifications would therefore be expected to alter these parameters. In the present study, we review mechanisms of oxidative damage to ECM, resulting changes in matrix structure and how this affects cellular behaviour. The role of such damage in the development and progression of inflammatory diseases is also discussed with particular reference to cardiovascular disease.

KW - Antioxidants

KW - Cardiovascular Diseases

KW - Disease Progression

KW - Extracellular Matrix

KW - Heparan Sulfate Proteoglycans

KW - Humans

KW - Oxidants

KW - Oxidation-Reduction

KW - Oxidative Stress

KW - Reactive Nitrogen Species

KW - Reactive Oxygen Species

U2 - 10.1042/BST0391279

DO - 10.1042/BST0391279

M3 - Journal article

C2 - 21936802

VL - 39

SP - 1279

EP - 1287

JO - Biochemical Society Transactions

JF - Biochemical Society Transactions

SN - 0300-5127

IS - 5

ER -