Title:Dysfunctional High-density Lipoprotein: The Role of Myeloperoxidase and Paraoxonase-1
Volume: 28
Issue: 14
Author(s): Tiziana Bacchetti, Gianna Ferretti*, Federico Carbone, Stefano Ministrini, Fabrizio Montecucco, Tannaz Jamialahmadi and Amirhossein Sahebkar*
Affiliation:
- Department of Clinical Science and Odontostomatology, Polytechnic University of Marche, Ancona,Italy
- Halal Research Center of IRI, FDA, Tehran,Iran
Keywords:
High-density lipoprotein, Myeloperoxidase, Paraoxonase, Atherosclerosis, metabolic syndrome, HDL
activity.
Abstract: 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 leukocyte-
derived enzyme myeloperoxidase (MPO) has recently attracted great interest as it catalyzes
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 activity,
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.
