Dysfunctional high-density lipoprotein: The role of myeloperoxidase and paraoxonase-1

Tiziana Bacchetti, Gianna Ferretti, Federico Carbone, Stefano Ministrini, Fabrizio Montecucco, Tannaz Jamialahmadi, Amirhossein Sahebkar

Research output: Contribution to journalReview articlepeer-review


Low circulating high-density lipoproteins (HDL) are not only defining criteria for metabolic syndrome, but are more generally associated with atherosclerotic cardiovascular disease (ASCVD) and other chronic diseases. Oxidative stress, a hallmark of cardio-metabolic disease, further influences HDL activity by suppressing their function. Especially the leuko-cyte-derived enzyme myeloperoxidase (MPO) has recently attracted great interest as it cata-lyzes the formation of oxidizing reactive species that modify the structure and function of HDL, ultimately increasing cardiovascular risk. Contrariwise, paraoxonase-1 (PON1) is an HDL-associated enzyme that protects HDL from lipid oxidation and then acts as a protective factor against ASCVD. It is noteworthy that recent studies have demonstrated how MPO, PON1 and HDL form a functional complex in which PON1 partially inhibits the MPO activ-ity, while MPO in turn partially inactivates PON1.In line with that, a high MPO/PON1 ratio characterizes patients with ASCVD and metabolic syndrome and has been suggested as a potential marker of dysfunctional HDL as well as a predictor of ASCVD. In this review, we summarize the evidence on the interactions between MPO and PON1 with regard to their structure, function and interaction with HDL activity. We also provide an overview of in vitro and experimental animal models, finally focusing on clinical evidence from a cohort of patients with ASCVD and metabolic syndrome.

Original languageEnglish
Pages (from-to)2842-2850
Number of pages9
JournalCurrent Medicinal Chemistry
Issue number14
Publication statusPublished - 2021


  • Atherosclerosis
  • HDL activity
  • High-density lipoprotein
  • Metabolic syndrome
  • Myeloperoxidase
  • Paraoxonase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry


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