Gender-specific correlation between plasma myeloperoxidase levels and serum high-density lipoprotein-associated paraoxonase-1 levels in patients with stable and unstable coronary artery disease

Atherosclerosis. 2013 Dec;231(2):308-14. doi: 10.1016/j.atherosclerosis.2013.08.037. Epub 2013 Oct 8.

Abstract

Objective: Low high-density lipoprotein (HDL) cholesterol is well-established as a negative risk factor for coronary artery disease (CAD) and its anti-oxidant property has been attributed mainly to the HDL-bound enzyme paraoxonase-1 (PON-1). Recently, myeloperoxidase (MPO), a pro-oxidant enzyme released from activated neutrophils, has been shown to alter the atheroprotective function of HDL to a dysfunctional form. This study investigated the relationship between plasma MPO and serum PON-1 levels in patients with stable (SAP) and unstable angina pectoris (UAP).

Methods: Plasma MPO levels and serum PON-1 concentration/activity were measured in patients with SAP (n = 226), UAP (n = 151) and in control subjects (n = 99).

Results: Plasma MPO levels in UAP patients were significantly higher than those in SAP patients or in control subjects (UAP, 21.6[16.7-44.6]; SAP, 19.3[15.7-29.1]; control, 15.9[14.7-18.7] ng/mL; P < 0.0001). Serum PON-1 concentrations in UAP and SAP patients were significantly lower than those in control subjects (UAP, 55.6[45.9-69.7]; SAP, 55.0[46.9-64.9]; control, 62.5[51.1-78.8] μg/mL; P = 0.0002). Plasma MPO levels showed a weak inverse correlation with serum PON-1 concentrations in all subjects (R = -0.163, P < 0.0005). Moreover, in women, plasma MPO levels showed a significant inverse correlation with serum PON-1 concentrations and PON-arylesterase activity in SAP (concentration: R = -0.537, P < 0.0001; arylesterase-activity: R = -0.469, P < 0.001) and UAP (concentration: R = -0.340, P < 0.05; arylesterase-activity: R = -0.350, P < 0.05) patients, but not in men.

Conclusion: This study demonstrates that plasma MPO levels have a significant inverse correlation with PON-1 levels, especially in women, in SAP and UAP patients, and suggests that an imbalance between pro-oxidants and anti-oxidants may contribute to the progression of coronary plaque instability.

Keywords: Angina; Myeloperoxidase; Oxidative stress; Paraoxonase.

MeSH terms

  • Aged
  • Angina, Stable / blood*
  • Angina, Unstable / blood*
  • Antioxidants / metabolism
  • Aryldialkylphosphatase / blood*
  • Biomarkers / blood
  • Case-Control Studies
  • Coronary Artery Disease / blood*
  • Diabetes Complications
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Lipoproteins, HDL / blood*
  • Male
  • Middle Aged
  • Oxidants / metabolism
  • Oxidative Stress
  • Peroxidase / blood*
  • Polymorphism, Genetic
  • Sex Factors

Substances

  • Antioxidants
  • Biomarkers
  • Lipoproteins, HDL
  • Oxidants
  • Peroxidase
  • Aryldialkylphosphatase
  • PON1 protein, human