Myeloperoxidase secreted by macrophages and neutrophils in atherosclerotic lesions generates a tyrosyl radical in apolipoprotein (apo) AI, a major protein component of high-density lipoprotein (HDL), thus inducing the formation of apoAI-apoAII heterodimers. It can also cause nitration and chlorination of tyrosine residues. Determining the apoAI-apoAII heterodimer could provide useful information as to functional changes in HDL and/or the progression of atherosclerotic lesions. To this end, the apoAI-apoAII heterodimer was identified in normal human serum by immunoblotting; the band intensity was increased by treatment with myeloperoxidase. This apparent increase in heterodimer formation was quantitatively confirmed by ELISA. In normal human serum, a significant correlation between the concentrations of apoAI-apoAII heterodimer and free apoAII (r=0.763), but not free apoAI (r=0.093), was observed, indicating that heterodimer formation is likely induced on HDL particles carrying both apoAI and apoAII (Lp-AI/AII). In preliminary studies, the levels of apoAI-apoAII heterodimer were statistically higher in plasma from subjects with acute myocardial infarction (AMI) as compared to controls. These findings indicate the possibility that the apoAI-apoAII heterodimer, including nitration and chlorination modifications, may serve as an indicator of atherosclerotic lesions.
Apolipoprotein A-I Apolipoprotein A-II