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ApoA-I/HDL-C levels are inversely associated with abdominal aortic aneurysm progression

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245

Theme Issue
Venous thromboembolism

Issue: 2015: 113/6 (June) pp. 1159–1382
Pages: 1335-1346
Ahead of Print: 2015-03-19

ApoA-I/HDL-C levels are inversely associated with abdominal aortic aneurysm progression

Online Supplementary Material

E. Burillo (1), J. S. Lindholt (2), P. Molina-Sánchez (3), I. Jorge (4), R. Martinez-Pinna (1), L. M. Blanco-Colio (1), C. Tarin (1), M. M. Torres-Fonseca (1), M. Esteban (5), J. Laustsen (2), P. Ramos-Mozo (1), E. Calvo (4), J. A. Lopez (4), M. Vega de Ceniga (6), J.-B. Michel (7), J. Egido (1, 8), V. Andrés (3), J. Vazquéz (4), O. Meilhac (7, 9), J. L. Martin-Ventura (1)

(1) Vascular Research Lab, IIS-Fundación Jiménez Diaz-Autonoma University, Madrid, Spain; (2) Departments of Cardiovascular and Thoracic Surgery, University Hospitals of Odense, Viborg and Aarhus, Denmark; (3) Molecular and Genetic Cardiovascular Pathophysiology Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; (4) Cardiovascular Proteomics Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; (5) Hospital de Cruces, Vizcaya, Spain; (6) Hospital de Galdakao, Vizcaya, Spain; (7) Inserm, U1148, Univ Paris 7, CHU X-Bichat, Paris, France; (8) Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain; (9) CHU de La Réunion, Saint-Denis, France


proteomics, lipoproteins, Abdominal aortic aneurysm, vascular remodelling


Abdominal aortic aneurysm (AAA) evolution is unpredictable, and there is no therapy except surgery for patients with an aortic size> 5 cm (large AAA). We aimed to identify new potential biomarkers that could facilitate prognosis and treatment of patients with AAA. A differential quantitative proteomic analysis of plasma proteins was performed in AAA patients at different stages of evolution [small AAA (aortic size=3–5cm) vs large AAA] using iTRAQ labelling, high-throughput nano-LC-MS/MS and a novel multi-layered statistical model. Among the proteins identified, ApoA-I was decreased in patients with large AAA compared to those with small AAA. These results were validated by ELISA on plasma samples from small (n=90) and large AAA (n=26) patients (150± 3 vs 133± 5 mg/dl, respectively, p< 0.001). ApoA-I levels strongly correlated with HDL-Cholesterol (HDL-C) concentration (r=0.9, p< 0.001) and showed a negative correlation with aortic size (r=-0.4, p< 0.01) and thrombus volume (r=-0.3, p< 0.01), which remained significant after adjusting for traditional risk factors. In a prospective study, HDL-C independently predicted aneurysmal growth rate in multiple linear regression analysis (n=122, p=0.008) and was inversely associated with need for surgical repair (Adjusted hazard ratio: 0.18, 95 % confidence interval: 0.04–0.74, p=0.018). In a nation-wide Danish registry, we found lower mean HDL-C concentration in large AAA patients (n=6,560) compared with patients with aorto-iliac occlusive disease (n=23,496) (0.89± 2.99 vs 1.59± 5.74 mmol/l, p< 0.001). Finally, reduced mean aortic AAA diameter was observed in AngII-infused mice treated with ApoA-I mimetic peptide compared with saline-injected controls. In conclusion, ApoA-I/HDL-C systemic levels are negatively associated with AAA evolution. Therapies targeting HDL functionality could halt AAA formation.

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