title: 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.
authors: Elena
authors: E
authors: Burillo
authors: Prof. Jes S. Lindholt, DMSci, PhD, Department of Thoracic, Heart and Vascular Surgery T, University Hospital of Odense, J. B. Winsløwsvej 5, Odense 5000 C, Denmark, E-mail: Jes.sanddal.lindholt@ouh.regionsyddanmark.dk.
authors: Jes S
authors: JS
authors: Lindholt
authors: Pedro
authors: P
authors: Molina-Sánchez
authors: Immaculada
authors: I
authors: Jorge
authors: Roxana
authors: R
authors: Martinez-Pinna
authors: Luis Miguel
authors: LM
authors: Blanco-Colio
authors: Carlos
authors: C
authors: Tarin
authors: Monica Maria
authors: MM
authors: Torres-Fonseca
authors: Margarita
authors: M
authors: Esteban
authors: Jesper
authors: J
authors: Laustsen
authors: Priscilla
authors: P
authors: Ramos-Mozo
authors: Enrique
authors: E
authors: Calvo
authors: Juan Antonio
authors: JA
authors: Lopez
authors: Melina
authors: M
authors: Vega de Ceniga
authors: Jean-Baptiste
authors: JB
authors: Michel
authors: Jesus
authors: J
authors: Egido
authors: Vicente
authors: V
authors: Andrés
authors: Jesús
authors: J
authors: Vazquéz
authors: Olivier
authors: O
authors: Meilhac
authors: Jose Luis Martin-Ventura, PhD, Vascular Research Lab, IIS-Fundacion Jimenez Diaz-Autonoma University, Avenida de los Reyes Católicos, 2, 28040 Madrid, Spain, Tel.: +34 91 5504800 (ext. 3168), E-mail: jlmartin@fjd.es.
authors: Jose Luis
authors: JL
authors: Martin-Ventura
mesh_terms: D000368:Aged; D000804:Angiotensin II; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000097:blood* / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D016632:Apolipoprotein A-I / Q000097:blood* / Q000494:pharmacology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D002853:Chromatography, Liquid; D003718:Denmark; D004195:Disease Models, Animal; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018716:Molecular Mimicry; D015999:Multivariate Analysis; D036103:Nanotechnology; D010455:Peptides / Q000494:pharmacology; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D040901:Proteomics / Q000379:methods; D012042:Registries; D013030:Spain; D053719:Tandem Mass Spectrometry
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D015415:Biomarkers; D008076:Cholesterol, HDL; D010455:Peptides; D000804:Angiotensin II
keywords: Vascular remodelling; abdominal aortic aneurysm; lipoproteins; proteomics