Alteration of HDL functionality and PON1 activities in acute coronary syndrome patients

Objective: The functionality of HDL has been suggested as an important factor in the prevention of cardiovascular and coronary artery diseases. The objective of the present study was to investigate the functionality of HDL and the factors that may affect the anti-atherogenic properties of HDL in ACS patients. Methods and results: One hundred healthy subjects and 205 ACS patients were recruited. HDL functionality was evaluated by measuring their capacity to mediate cholesterol efflux from J774 macrophages. Oxidative stress status was determined by measuring plasma malondialdehyde (MDA), protein carbonyl, and vitamin E levels by HPLC. The PON1 Q192R polymorphism status and PON1 paraoxonase and arylesterase activities of the healthy subjects and ACS patients were also determined. The HDL of ACS patients displayed a limited capacity to mediate cholesterol efflux, especially via the ABCA1-pathway. MDA (7.06 ± 0.29. μM) and protein carbonyl (9.29 ± 0.26. μM) levels were significantly higher in ACS patients than in healthy subjects (2.29 ± 0.21. μM and 3.07 ± 0.17. μM, respectively, p. <. 0.0001), while α- and γ-tocopherol (vitamin E) levels in ACS patients were 8-fold (p. <. 0.001) and 2-fold (p. <. 0.05) lower than in healthy subjects. Paraoxonase, arylesterase and HDL-corrected PON1 activities (PON1 activity/HDL ratio) were significantly lower in ACS patients. Logistic regression analyses showed that high PON1 paraoxonase and arylesterase activities had a significant protective effect (OR = 0.413, CI 0.289-0.590, p. <. 0.001; OR = 0.232 CI 0.107-0.499, p. <. 0.001, respectively) even when adjusted for HDL level, age, BMI, and PON1 polymorphism. Conclusion: The results of the present study showed that the functionality of HDL is impaired in ACS patients and that the impairment may be due to oxidative stress and an alteration of PON1 activities.