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

Abstract：

: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=3-5 cm) 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.

journal_name

Thromb Haemost

journal_title

Thrombosis and haemostasis

authors

Burillo E,Lindholt JS,Molina-Sánchez P,Jorge I,Martinez-Pinna R,Blanco-Colio LM,Tarin C,Torres-Fonseca MM,Esteban M,Laustsen J,Ramos-Mozo P,Calvo E,Lopez JA,Vega de Ceniga M,Michel JB,Egido J,Andrés V,Vazquéz J,Meilha

doi

10.1160/TH14-10-0874

subject

Has Abstract

pub_date

2015-06-01 00:00:00

pages

1335-46

issue

eissn

0340-6245

issn

2567-689X

pii

14-10-0874

journal_volume

113

pub_type

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