Thromb Haemost 2018; 118(06): 1088-1100
DOI: 10.1055/s-0038-1645857
Atherosclerosis and Ischaemic Disease
Schattauer GmbH Stuttgart

Antibodies against HDL Components in Ischaemic Stroke and Coronary Artery Disease

Joana R. Batuca
1  CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisboa, Portugal
,
Marta C. Amaral
1  CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisboa, Portugal
2  Department of Medicine IV, Immune-mediated Systemic Diseases Unit, Fernando Fonseca Hospital, Amadora, Portugal
,
Catarina Favas
2  Department of Medicine IV, Immune-mediated Systemic Diseases Unit, Fernando Fonseca Hospital, Amadora, Portugal
,
Gonçalo C. Justino
3  Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal
,
Ana L. Papoila
4  CEAUL, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisboa, Portugal
,
Paul R. J. Ames
1  CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisboa, Portugal
,
José Delgado Alves
1  CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisboa, Portugal
2  Department of Medicine IV, Immune-mediated Systemic Diseases Unit, Fernando Fonseca Hospital, Amadora, Portugal
› Author Affiliations
Funding This work was funded by a grant from AstraZeneca Foundation Portugal, by www.fondazioneaps.org, Italy and by Portuguese Foundation for Science and Technology (FCT) via the post-doctoral SFRH/BPD/112411/2015 and iNOVA4Health - UID/Multi/04462/2013, and co-funded by FEDER under the PT2020 Partnership Agreement.
Further Information

Publication History

12 October 2017

21 March 2018

Publication Date:
03 May 2018 (online)

Abstract

Quantitative and qualitative defects of high-density lipoprotein (HDL) are important in atherogenesis. In this study, we investigated whether antibodies against HDL components had additional value to conventional cardiovascular risk factors for the diagnosis of ischaemic stroke (IS) and coronary artery disease (CAD). Cross-sectional study was conducted on 53 patients with IS, 51 with CAD and 55 healthy controls, and in vitro studies to validate findings of the clinical study. We determined serum immunoglobulin G (IgG) antibodies against HDL (aHDL), apolipoproteins (aApoA-I, aApoA-II and aApoC-I) and paraoxonase-1 (aPON1) as well as PON1 activity (PON1a), total antioxidant capacity and biomarkers of endothelial activation (serum nitric oxide metabolites, 3-nitrotyrosine, VCAM-1 and ICAM-1); in vitro assays tested the capacity of IgG aHDL purified from high titer patients to inhibit PON1a and to reverse protective effect of HDL on endothelial cells. IgG aHDL, aApoA-I and aPON1 were higher in IS and CAD than controls (p < 0.001), predicted negatively PON1a and positively VCAM-1 and ICAM-1. By adding IgG aHDL and aApoA-I to a traditional cardiovascular risk factors model for IS and by adding IgG aHDL in a similar model for CAD, we obtained better discrimination of IS and CAD from healthy controls. IgG aHDL purified from IS and CAD inhibited PON1a by 38% (p < 0.01) and abrogated the protective effect of HDL on VCAM-1 expression by 126% compared with non-specific human IgG (p < 0.001). IgG against HDL components interfere with the antioxidant and anti-inflammatory properties of HDL and may represent novel biomarkers for vascular disease that need to be investigated in prospective studies.

Supplementary Material