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Dysfunctional High-density Lipoprotein: The Role of Myeloperoxidase and Paraoxonase-1

Author(s):

Tiziana Bacchetti, Gianna Ferretti, Federico Carbone, Stefano Ministrini, Fabrizio Montecucco, Tannaz Jamialahmadi and Amirhossein Sahebkar*   Pages 1 - 9 ( 9 )

Abstract:


Low circulating high-density lipoproteins (HDL) are not only a 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. Noteworthy, 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, 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 on in vitro and experimental animal models, finally focusing on clinical evidence from cohort of patients with ASCVD and metabolic syndrome.

Keywords:

High-density lipoprotein, Myeloperoxidase, Paraoxonase, Atherosclerosis, metabolic syndrome, HDL activity

Affiliation:

Department of Life and Environmental Sciences (DiSVA), Polytechnic University of Marche, Ancona, Department of Clinical Science and Odontostomatology, Polytechnic University of Marche, Ancona, First Clinic of Internal Medicine Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Internal Medicine Department, "Santa Maria della Misericordia" Hospital, University of Perugia, Piazzale Menghini, Sant'Andrea delle Fratte, 06132, Perugia, IRCCS Ospedale Policlinico San Martino Genoa – Italian Cardiovascular Network, 10 Largo Benzi, 16132 Genoa, Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Halal Research Center of IRI, FDA, Tehran



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