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

Abstract

gamma-Glutamyl-semialdehyde (gammaGSA) is a major product of the metal catalysed oxidation of apolipoprotein B-100 (apoB-100) proline and arginine residues. On reduction, gammaGSA forms 5-hydroxy-2-aminovaleric acid (HAVA). This report describes the application of HAVA measurement to characterise the formation of gammaGSA 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.

Figure 1

Box plots showing low density lipoprotein apolipoprotein B-100 (apoB-100) 5-hydroxy-2-aminovaleric acid (HAVA) content in intima from various stages of lesion evolution in human thoracic aorta.