Exposure of tropoelastin to peroxynitrous acid gives high yields of nitrated tyrosine residues, di-tyrosine cross-links and altered protein structure and function.

Elastin is an abundant extracellular matrix protein in elastic tissues, including the lungs, skin and arteries, and comprises 30-57% of the aorta by dry mass. The monomeric precursor, tropoelastin (TE), undergoes complex processing during elastogenesis to form mature elastic fibres. Peroxynitrous acid (ONOOH), a potent oxidising and nitrating agent, is formed in vivo from superoxide and nitric oxide radicals.

Peroxynitrite-mediated oxidation of plasma fibronectin.

Fibronectin is a large dimeric glycoprotein present in both human plasma and in basement membranes. The latter are specialized extracellular matrices underlying endothelial cells in the artery wall. Peroxynitrous acid (ONOOH) a potent oxidizing and nitrating agent, is formed in vivo from superoxide and nitric oxide radicals by stimulated macrophages and other cells.

Peroxynitrous acid induces structural and functional modifications to basement membranes and its key component, laminin.

Basement membranes (BM) are specialized extracellular matrices underlying endothelial cells in the artery wall. Laminin, the most abundant BM glycoprotein, is a structural and biologically active component. Peroxynitrous acid (ONOOH), a potent oxidizing and nitrating agent, is formed in vivo at sites of inflammation from superoxide and nitric oxide radicals.

Oxidation modifies the structure and function of the extracellular matrix generated by human coronary artery endothelial cells.

ECM (extracellular matrix) materials, such as laminin, perlecan, type IV collagen and fibronectin, play a key role in determining the structure of the arterial wall and the properties of cells that interact with the ECM. The aim of the present study was to investigate the effect of peroxynitrous acid, an oxidant generated by activated macrophages, on the structure and function of the ECM laid down by HCAECs (human coronary artery endothelial cells) in vitro and in vivo. We show that exposure of HCAEC-derived native matrix components to peroxynitrous acid (but not decomposed oxidant) at concentrations >1 μM results in a loss of antibody recognition of perlecan, collagen IV, and cell-binding sites on laminin and fibronectin.

Mechanisms and consequences of oxidative damage to extracellular matrix.

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.