PARAOXONASE 1 ENZYME ACTIVITY AND MYELOPEROXIDASE CONCENTRATION IN INDIVIDUALS WITH ANGIOGRAPHICALLY CONFIRMED CORONARY ARTERY DISEASE
Keywords:
coronary arthery disease, HDL cholesterol, PON1 MPOAbstract
Introduction: PON1 and MPO are key regulators of HDL function. While PON1 exerts antiatherogenic protection by limiting lipid oxidation, MPO promotes HDL oxidation and the formation of dysfunctional, pro-inflammatory HDL.
Aim: This study aimed to evaluate the relationship between PON1 catalytic activity and MPO concentration with the development and severity of atherosclerosis and coronary artery disease in patients from the Republic of North Macedonia.
Material and methods: This cross-sectional study included subjects undergoing percutaneous coronary angiography with or without stenting due to monitoring of stable angina or induced ischemia. The catalytic activity of the PON1 enzyme and the concentration of the MPO enzyme were analyzed. The PON1 catalytic activity was measured spectrophotometrically, MPO levels were measured with a human MPO ELISA test kit.
Results: A total of 165 subjects (106 CAD, 59 non-CAD) were analyzed. CAD patients had significantly lower PON1 activity, whereas MPO levels did not differ. MPO/PON1 ratio and HDL×PON1 index clearly discriminated CAD from non-CAD. CAD patients showed lower HDL and ApoA1 and higher glucose and Lp(a). Across CAD severity stratification (no stent, stent, restenosis), LDL and triglycerides were similar, while Lp(a) increased and HDL×PON1 declined, indicating progressive HDL dysfunction and oxidative imbalance.
Conclusion: Our findings suggest that CAD was associated with lower PON1 activity, reflecting dysfunctional and pro-oxidative HDL despite similar LDL levels. Lp(a) increased with atherosclerosis severity and was highest in patients with restenosis, highlighting the value of combined biochemical testing for enhanced cardiovascular risk stratification and early identification of susceptibility in the Macedonian population.
References
Précourt LP, Amre D, Denis MC, Lavoie JC, Delvin E, Seidman E, et al. The three-gene paraoxonase family: physiologic roles, actions and regulation. Atherosclerosis 2011; 214(1): 20-36. doi: 10.1016/j.atherosclerosis.2010.08.076.
Mackness MI, Arrol S, Durrington PN. Paraoxonase prevents accumulation of lipoperoxides in low-density lipoprotein. FEBS Lett 1991; 286(1-2): 152-154. doi: 10.1016/0014-5793(91)80962-3.
Mackness MI, Abbott CA, Arrol S, Durrington PN. The role of highdensity lipoprotein and lipid-soluble antioxidant vitamins in inhibiting low-density lipoprotein oxidation. Biochem J 1993; 294( Pt 3)(Pt 3): 829-834. doi: 10.1042/bj2940829.
Mackness MI, Arrol S, Abbott CA, Durrington PN. Protection of low-density lipoprotein against oxidative modification by high-density lipoprotein associated paraoxonase. Atherosclerosis 1993; 104(1-2): 129-135. doi: 10.1016/0021-9150(93)90183-u.
Watson AD, Berliner JA, Hama SY, La Du BN, Faull KF, Fogelman AM, et al. Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. J Clin Invest 1995; 96(6): 2882-2891. doi: 10.1172/JCI118359.
Aviram M, Billecke S, Sorenson R, Bisgaier C, Newton R, Rosenblat M, et al. Paraoxonase active site required for protection against LDL oxidation involves its free sulfhydryl group and is different from that required for its arylesterase/paraoxonase activities: selective action of human paraoxonase allozymes Q and R. Arterioscler Thromb Vasc Biol 1998; 18(10): 1617-1624. doi: 10.1161/01.atv.18.10.1617.
Shunmoogam N, Naidoo P, Chilton R. Paraoxonase (PON)-1: a brief overview on genetics, structure, polymorphisms and clinical relevance. Vasc Health Risk Manag 2018; 14: 137-143. doi: 10.2147/VHRM.S165173
Murillo-González FE, Ponce-Ruiz N, Rojas-García AE, Rothenberg SJ, Bernal-Hernández YY, Cerda-Flores RM, et al. PON1 lactonase activity and its association with cardiovascular disease. Clin Chim Acta 2020; 500: 47-53. doi: 10.1016/j.cca.2019.09.016.
Brennan ML, Penn MS, Van Lente F, Nambi V, Shishehbor MH, Aviles RJ, et al. Prognostic value of myeloperoxidase in patients with chest pain. N Engl J Med 2003; 349(17): 1595-1604. doi: 10.1056/NEJMoa035003.
Varadhan S, Venkatachalam R, Perumal SM, Ayyamkulamkara SS. Evaluation of Oxidative Stress Parameters and Antioxidant Status in Coronary Artery Disease Patients. Arch Razi Inst 2022; 77(2):853-859. doi: 10.22092/ARI.2022.357069.1965.
Mazur A. An enzyme in animal tissues capable of hydrolysing the phosphorus-fluorine bond of alkyl fluorophosphates. J Biol Chem 1946; 164: 271-289. PMID: 20989488.
Aldridge WN. Serum esterases 2-An enzyme hydrolysing diethyl p-nitrophenylphosphate (E600) and its identity with the A-esterase of mammalian sera. Biochem J 1953; 53(1): 117-124. doi: 10.1042/bj0530117.
Mackness M, Mackness B. Human Paraoxonase-1 (PON1): gene structure and expression, promiscuous activities and multiple physiological roles. Gene 2015; 567(1): 12-21. doi: 10.1016/j.gene.2015.04.088.
Draganov DI, Stetson PL, Watson CE, Billecke SS, La Du BN. Rabbit serum paraoxonase 3 (PON3) is a high density lipoprotein-associated lactonase and protects low density lipoprotein against oxidation. J Biol Chem 2000; 275(43): 33435-33442. doi: 10.1074/jbc.M004543200.
Taler-Verčič A, Goličnik M, Bavec A. The Structure and Function of Paraoxonase-1 and Its Comparison to Paraoxonase-2 and -3. Molecules 2020; 25(24): 5980. doi: 10.3390/molecules25245980.
Petrič B, Kunej T, Bavec A. A Multi-Omics Analysis of PON1 Lactonase Activity in Relation to Human Health and Disease. OMICS 2021; 25(1): 38-51. doi: 10.1089/omi.2020.0160.
Teng N, Maghzal GJ, Talib J, Rashid I, Lau AK, Stocker R. The roles of myeloperoxidase in coronary artery disease and its potential implication in plaque rupture. Redox Rep 2017; 22(2): 51-73. doi: 10.1080/13510002.2016.1256119.
Khan AA, Alsahli MA, Rahmani AH. Myeloperoxidase as an Active Disease Biomarker: Recent Biochemical and Pathological Perspectives. Medical sciences (Basel, Switzerland) 2018; 6(2): 33. doi: 10.3390/medsci6020033.
Daugherty A, Dunn JL, Rateri DL, Heinecke JW. Myeloperoxidase, a catalyst for lipoprotein oxidation, is expressed in human atherosclerotic lesions. J Clin Invest 1994; 94(1): 437-444. doi: 10.1172/JCI117342.
Wang G, Mathew AV, Yu H, Li L, He L, Gao W, et al. Myeloperoxidase mediated HDL oxidation and HDL proteome changes do not contribute to dysfunctional HDL in Chinese subjects with coronary artery disease. PLoS One 2018; 13(3): e0193782. doi: 10.1371/journal.pone.0193782.
Baldus S, Heeschen C, Meinertz T, Zeiher AM, Eiserich JP, Münzel T, et al. Myeloperoxidase Serum Levels Predict Risk in Patients With Acute Coronary Syndromes. Circulation 2003; 108(12): 1440-1445. doi: 10.1161/01.CIR.0000090690. 67322.51.
Heinecke JW. The HDL proteome: a marker--and perhaps mediator--of coronary artery disease. J Lipid Res 2009; 50 Suppl(Suppl): S167-S171. doi: 10.1194/jlr.R800097-JLR200.
Huang J, Yancey PG, Tao H, Borja MS, Smith LE, Kon V, et al. Reactive Dicarbonyl Scavenging Effectively Reduces MPO-Mediated Oxidation of HDL and Restores PON1 Activity. Nutrients 2020; 12(7): 1937. doi: 10.3390/nu12071937.
Brunzell JD, Davidson M, Furberg CD, Goldberg RB, Howard BV, Stein JH, et al. Lipoprotein management in patients with cardiometabolic risk: consensus statement from the American Diabetes Association and the American College of Cardiology Foundation. Diabetes Care 2008; 31(4): 811-822. doi: 10.2337/dc08-9018.
Durrington PN, Mackness B, Mackness MI. Paraoxonase and atherosclerosis. Arterioscler Thromb Vasc Biol 2001; 21(4): 473-480. doi: 10.1161/01.atv.21.4.473.
Tward A, Xia YR, Wang XP, Shi YS, Park C, Castellani LW. Decreased atherosclerotic lesion formation in human serum paraoxonase transgenic mice. Circulation 2002; 106(4): 484-490. doi: 10.1161/01.cir.0000023623.87083.4f.
Shokri Y, Variji A, Nosrati M, Khonakdar-Tarsi A, Kianmehr A, Kashi Z, et al. Importance of paraoxonase 1 (PON1) as an antioxidant and antiatherogenic enzyme in the cardiovascular complications of type 2 diabetes: Genotypic and phenotypic evaluation. Diabetes Res Clin Pract 2020; 161: 108067. doi: 10.1016/j.diabres. 2020.108067.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Katerina Krsteva Jakimovska, Marija Vavlukis, Oliver Bushljetic, Sonja Topuzovska
This work is licensed under a Creative Commons Attribution 4.0 International License.
This work is licensed under CC BY 4.0 
