Association of Ficolin-3 with abdominal aortic aneurysm presence and progression

Carlos-Ernesto Fernandez-García, Elena Burillo, Jes S Lindholt, Diego Martinez-Lopez, Katrine Pilely, Carla Mazzeo, Jean-Baptiste Michel, Jesus Egido, Peter Garred, Luis M Blanco-Colio, Jose L Martin-Ventura

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Abstrakt

BACKGROUND: Abdominal aortic aneurysm (AAA) patients are usually asymptomatic and AAA evolution is unpredictable. Ficolin-3, mainly synthesized by the liver, is a molecule of the lectin complement-activation pathway involved in AAA pathophysiology.

OBJECTIVES: To define extrahepatic sources of ficolin-3 in AAA, and investigate the role of ficolin-3 as a biomarker of AAA presence and progression.

METHODS: Microvesicles (exosomes and microparticles) were isolated from culture conditioned medium of ADP-activated platelets, as well as from AAA tissue-conditioned medium (thrombus and wall). Ficolin-3 levels were analyzed by western-blot, real-time PCR, immunohistochemistry and ELISA.

RESULTS: Increased Ficolin-3 levels were observed in microvesicles isolated from activated platelets. Similarly, microvesicles released from AAA tissue display increased ficolin-3 levels as compared with those from healthy tissue. Moreover, ficolin-3 mRNA levels in AAA wall were greatly increased compared with healthy aortic walls. Immunohistochemistry of AAA tissue demonstrated increased ficolin-3, while little staining was present in healthy walls. Finally, increased ficolin-3 levels were observed in AAA patients' plasma (n=478) compared with control plasma (n=176), which persisted after adjustment for risk factors [Adj. OR=5.29 (95% CI.:3.27;8.57)]. Moreover, a positive association of ficolin-3 with aortic diameter (Rho=0.25) and need for surgical repair was observed, also after adjustment for potential confounding factors [Adj. HR=1.55 (95% CI: 1.11;2.15)].

CONCLUSIONS: In addition to its hepatic expression, Ficolin-3 may be released into the extracellular medium via microvesicles, by both activated cells and pathological AAA tissue. Ficolin-3 plasma levels are associated with AAA presence and progression, suggesting its potential role as a biomarker of AAA. This article is protected by copyright. All rights reserved.

OriginalsprogEngelsk
TidsskriftJournal of Thrombosis and Haemostasis
Vol/bind15
Udgave nummer3
Sider (fra-til)575–585
ISSN1538-7933
DOI
StatusUdgivet - 2017

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