PON1 status is influenced by oxidative stress and inflammation in coronary heart disease patients

Jelena Kotur-Stevuljevic, Slavica Spasic, Zorana Jelic-Ivanovic, Vesna Spasojevic-Kalimanovska, Aleksandra Stefanovic, Ana Vujovic, Lidija Memon, Dimitra Kalimanovska-Ostric
Clinical Biochemistry 2008, 41 (13): 1067-73

OBJECTIVES: High-density lipoprotein (HDL) associated paraoxonase 1 (PON1) is an essential component of HDLs' capability to protect low-density lipoproteins (LDL) from oxidative modification and thus to limit the atherosclerotic process. The aim of the current study was to investigate the association between oxidative stress status, indices of inflammation and PON1 status parameters.

DESIGN AND METHODS: We determined the relationship between the oxidative stress status, inflammatory markers and PON1 status parameters in 261 middle-aged subjects: 156 coronary heart disease (CHD) patients and 105 CHD-free subjects (as the control group). The PON1 status involved PON1 activity measurements towards two substrates: paraoxon (POase activity) and diazoxon (DZOase activity) and subsequent PON1(Q192R) activity phenotype determination.

RESULTS: A statistically significant greater malondialdehyde (MDA) concentration in the RR phenotype subjects compared to QQ subjects within the CHD group was apparent (P<0.05). Multiple linear regression analysis revealed an independent influence of plasmatic SOD activity (P<0.05) on POase values and MDA (P<0.01) and O(2)(-) (P<0.05) on DZOase values. Involvement of inflammatory markers (fibrinogen and hsCRP) in the regression model did not hinder the influence of SOD and MDA on POase and DZOase activities, respectively.

CONCLUSIONS: Our CHD patients were in a state of oxidative stress, which was most evident in the RR phenotype group. The QQ phenotype group is associated with the lowest oxidative stress status level and also with a better capacity for anti-oxidative protection. Oxidative stress in CHD patients is maintained by systemic low-grade inflammation, which results in PON1 enzymatic activity exhaustion. Therefore, deeper investigation of an effective anti-oxidative and anti-inflammatory therapy should be necessary in order to increase anti-oxidative potency and improve PON1 status of CHD patients.

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