Abstract 14032: Myeloperoxidase and Paraoxonase 1 Modulate Functional Quality of HDL and Progression of Coronary Artery Lesions

Abstract

Aims: It has been shown that granular leukocyte-derived myeloperoxidase (MPO) promotes oxidation of lipoproteins, while an HDL-associated enzyme paraoxonase 1 (PON1) has antioxidant properties for lipoproteins. Therefore, we evaluated effects of MPO and PON1 on functional quality of HDL and restenosis after percutaneous coronary intervention (PCI).

Methods and Results: Serum lipid profile, MPO level, and PON1 activity were determined in total 111 patients hospitalized for follow-up coronary angiography 6 months after PCI. Coronary restenosis was observed in 28 patients but not associated with conventional lipid profile including serum levels of LDL-C and HDL-C probably due to the intensive lipid-lowering treatments with statins. In contrast, serum MPO levels were 115% higher, and both PON1-paraoxonase and arylesterase activities were 70% lower in patients with restenosis than in those without restenosis (p<0.05). As a result, the high MPO/PON1 ratio, when cutoff values were set on 1.68 for MPO/paraoxonase and 5.03 for MPO/arylesterase, was independently correlated with restenosis (odds ratio 10.83, 13.45; 95% CI 1.68-69.5, 1.31-137.5; p=0.012, 0.028, respectively). Next, we isolated HDL from patients with high or low MPO/PON1 ratio, and compared anti-inflammatory properties of HDL by cell culture experiments. Human umbilical vein endothelial cells were stimulated with inflammatory cytokine in the presence or absence of HDL with different MPO/PON1 ratio, and the expression of vascular cell adhesion molecule-1 (VCAM-1) was evaluated by real-time PCR. HDL isolated from patients with low serum MPO/PON1 ratio inhibited VCAM-1 expression significantly greater than that with high MPO/PON1 ratio.

Conclusions: MPO and PON1 modulate the progression of coronary artery lesions through regulating functional quality of lipoproteins. These molecules could be a marker and modulator of the prevention of coronary artery disease.