Measurement of 5-hydroxy-2-aminovaleric acid as a specific marker of iron-mediated oxidation of proline and arginine residues of low density lipoprotein aplipoprotein B-100 in human atherosclerotic lesions

Gamma-Glutamyl-semialdehyde (Gamma-GSA) is a major product of the metal catalysed oxidation of apolipoprotein B-100 (apoB-100) proline and arginine residues. On reduction, Gamma-GSA forms 5-hydroxy-2-aminovaleric acid (HAVA). This report describes the application of HAVA measurement to characterise the formation of Gamma-GSA in low density lipoprotein (LDL) recovered from human atherosclerotic lesions. HAVA concentrations were greatly increased in LDL from early (mean, 10.25; SD, 3.49 mol/mol apoB-100; p < 0.01), intermediate (mean, 11.18; SD, 2.37 mol/mol apoB-100; p < 0.01), and advanced (mean, 9.91; SD, 2.15 mol/mol apoB-100; p < 0.01) lesions, when compared with LDL from normal aortic tissue (mean, 0.05; SD, 0.01 mol/mol apoB-100). These findings support the hypothesis that pathways involving metal catalysed oxidation of LDL apoB-100 are of pathological importance in atherogenesis. LDL apoB-100 recovered from human aortic vascular lesions. These observations provide quantitative chemical evidence for metal catalysed oxidative processes in the human artery wall.