Thiol-containing molecules interact with the myeloperoxidase/H2O2/chloride system to inhibit LDL oxidation

Pierre Van Antwerpen1, Karim Zouaoui Boudjeltia, Sajida Babar

  • 1Laboratory of Pharmaceutical Chemistry, Institute of Pharmacy, Université Libre de Bruxelles, Brussels, Belgium.

Insights

N-acetylcysteine (NAC) and its lysinate salt (NAL) effectively inhibit oxidized low-density lipoprotein (LDL) modification, a key factor in atheromatous plaque progression. These smaller thiol-containing molecules show greater efficacy than larger ones, suggesting potential therapeutic benefits.

Area of Science:

  • Cardiovascular Research
  • Biochemistry
  • Pharmacology

Background:

  • Oxidized low-density lipoproteins (LDL) contribute to vascular inflammation and atheromatous plaque development.
  • Myeloperoxidase (MPO) plays a crucial role in LDL oxidative modification within the vascular wall.
  • Inhibiting MPO's oxidative activity on apolipoprotein B-100 is a potential therapeutic strategy.

Purpose of the Study:

  • To evaluate the efficacy of thiol-containing molecules (glutathione, captopril, N-acetylcysteine (NAC), N-acetylcysteine lysinate (NAL)) in inhibiting MPO-mediated LDL oxidation.
  • To compare the inhibitory properties of these molecules with flufenamic acid, a known MPO inhibitor.

Main Methods:

  • In vitro assessment of MPO activity and its effect on LDL oxidation.
  • Comparison of inhibition efficacy among glutathione, captopril, NAC, NAL, and flufenamic acid.

Main Results:

  • Flufenamic acid inhibited MPO activity and HOCl production more effectively than thiol-containing molecules.
  • NAC and NAL demonstrated superior inhibition of LDL oxidative modification compared to captopril and glutathione.
  • The smaller size of NAC and NAL may contribute to their enhanced inhibitory effect on LDL oxidation.

Conclusions:

  • NAC and NAL are potent inhibitors of MPO-driven LDL oxidation.
  • The findings suggest NAC and NAL as promising candidates for pharmacological intervention in atherosclerosis.
  • Further in vivo studies are warranted to confirm the therapeutic relevance of these findings.

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