Serum paraoxonase-3 concentration is associated with insulin sensitivity in peripheral artery disease and with inflammation in coronary artery disease

Rull, Anna; García, Raúl; Fernández-Sender, Laura; García-Heredia, Anabel; Aragonès, Gerard; Beltrán-Debón, Raúl; Marsillach, Judit; Alegret, Josep M.; Martín-Paredero, Vicente; Mackness, Bharti; Mackness, Michael; Joven, Jorge; Camps, Jordi

doi:10.1016/j.atherosclerosis.2011.11.021

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Volume 220, Issue 2 , Pages 545-551, February 2012

Serum paraoxonase-3 concentration is associated with insulin sensitivity in peripheral artery disease and with inflammation in coronary artery disease

Anna Rull
- Centre de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, C. Sant Joan s/n, 43201 Reus, Catalonia, Spain
- These authors contributed equally to this work.
Raúl García
- Servei d’Angiologia, Cirurgia Vascular i Endovascular, Hospital Universitari Joan XXIII, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Tarragona, Catalonia, Spain
- These authors contributed equally to this work.
Laura Fernández-Sender
- Centre de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, C. Sant Joan s/n, 43201 Reus, Catalonia, Spain
Anabel García-Heredia
- Centre de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, C. Sant Joan s/n, 43201 Reus, Catalonia, Spain
Gerard Aragonès
- Centre de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, C. Sant Joan s/n, 43201 Reus, Catalonia, Spain
Raúl Beltrán-Debón
- Centre de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, C. Sant Joan s/n, 43201 Reus, Catalonia, Spain
Judit Marsillach
- Department of Genome Sciences, University of Washington, Seattle, WA, USA
Josep M. Alegret
- Unitat de Cardiologia, Hospital Universitari de Sant Joan, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Catalonia, Spain
Vicente Martín-Paredero
- Servei d’Angiologia, Cirurgia Vascular i Endovascular, Hospital Universitari Joan XXIII, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Tarragona, Catalonia, Spain
Bharti Mackness
- Centre de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, C. Sant Joan s/n, 43201 Reus, Catalonia, Spain
Michael Mackness
- Centre de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, C. Sant Joan s/n, 43201 Reus, Catalonia, Spain
Jorge Joven
- Centre de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, C. Sant Joan s/n, 43201 Reus, Catalonia, Spain
Jordi Camps
- Centre de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, C. Sant Joan s/n, 43201 Reus, Catalonia, Spain
- Corresponding author. Tel.: +34 977 310300; fax: +34 977 312569.

Received 6 July 2011; received in revised form 14 October 2011; accepted 14 November 2011. published online 09 December 2011.

Abstract

Objective

There are no data on the relationship between serum paraoxonase-3 (PON3) concentration and atherosclerosis in humans. Our aim was to investigate possible associations, using recently developed methods, in patients with peripheral artery disease (PAD) or coronary artery disease (CAD).

Methods

We studied 118 PAD and 72 CAD patients and 175 healthy volunteers. Serum PON3 was determined by in-house ELISA using polyclonal antibodies generated against a synthetic peptide with a sequence specific to PON3. Polymorphisms of the PON3 promoter were analysed by the Iplex Gold MassArray™ method.

Results

There was a significant increase in serum PON3 concentration in both groups of patients with respect to the control group. In PAD patients, we observed significant positive correlations between PON3, insulin levels and HOMA index. These associations were not observed in CAD. There were significant positive associations between serum PON3 and β-2-microglobulin, CCL2 and high-sensitivity C-reactive protein in CAD patients, but not in PAD. We did not find any significant differences in PON3 gene promoter polymorphisms and their haplotypes between patients and controls, indicating that associations were not genetically determined.

Conclusion

In both atherosclerotic phenotypes, serum PON3 concentration was increased, but this was associated with decreased insulin sensitivity in PAD and with inflammation in CAD.

Keywords: Antioxidants, Atherosclerosis, Lipoproteins, Myocardial infarction, Paraoxonases, Peripheral vascular disease