title: Association of ficolin-3 with abdominal aortic aneurysm presence and progression.
abstract: Essentials Abdominal aortic aneurysm (AAA) is asymptomatic and its evolution unpredictable. To find novel potential biomarkers of AAA, microvesicles are an excellent source of biomarkers. Ficolin-3 is increased in microvesicles obtained from activated platelets and AAA tissue. Increased ficolin-3 plasma levels are associated with AAA presence and progression.
  
  
  
  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 extra-hepatic sources of ficolin-3 in AAA and investigate the role of ficolin-3 as a biomarker of the presence and progression of AAA. 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 the AAA wall were greatly increased compared with healthy aortic walls. Immunohistochemistry of AAA tissue demonstrated increased ficolin-3, whereas 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 (adjusted odds ratio [OR], 5.29; 95% confidence interval [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 (adjusted hazard ratio, 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 the presence and progression of AAA, suggesting its potential role as a biomarker of AAA.
authors.affiliation: Vascular Research Laboratory, FIIS-Fundación Jiménez Díaz-Autonoma University, Madrid, Spain.
authors.forename: C-E
authors.initials: CE
authors.lastname: Fernandez-García
authors.affiliation: Vascular Research Laboratory, FIIS-Fundación Jiménez Díaz-Autonoma University, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Burillo
authors.affiliation: Department of Thoracic, Heart and Vascular Surgery, University Hospital of Odense, Odense, Denmark.
authors.forename: J S
authors.initials: JS
authors.lastname: Lindholt
authors.affiliation: Vascular Research Laboratory, FIIS-Fundación Jiménez Díaz-Autonoma University, Madrid, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Martinez-Lopez
authors.affiliation: Laboratory of Molecular Medicine, Department of Clinical Immunology, Sect.7631, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Pilely
authors.affiliation: Department of Cell Biology and Immunology, Molecular Biology Center/CSIC-UAM, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Mazzeo
authors.affiliation: Inserm, U1148, Université Paris 7, CHU X-Bichat, Paris, France.
authors.forename: J-B
authors.initials: JB
authors.lastname: Michel
authors.affiliation: Vascular Research Laboratory, FIIS-Fundación Jiménez Díaz-Autonoma University, Madrid, Spain.|Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Egido
authors.affiliation: Laboratory of Molecular Medicine, Department of Clinical Immunology, Sect.7631, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Garred
authors.affiliation: Vascular Research Laboratory, FIIS-Fundación Jiménez Díaz-Autonoma University, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.
authors.forename: L M
authors.initials: LM
authors.lastname: Blanco-Colio
authors.affiliation: Vascular Research Laboratory, FIIS-Fundación Jiménez Díaz-Autonoma University, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Martin-Ventura
mesh_terms: D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000737:chemistry; D003718:Denmark; D018450:Disease Progression; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D006973:Hypertension / Q000175:diagnosis; D037102:Lectins / Q000097:blood*; D008297:Male; D008403:Mass Screening; D008833:Microcirculation; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000175:diagnosis
chemical_list: D015415:Biomarkers; D017077:Culture Media, Conditioned; C109662:FCN3 protein, human; D006023:Glycoproteins; D037102:Lectins
keywords: aortic aneurysm, abdominal; biological markers; blood platelets; cell-derived microparticles; complement system proteins; exosomes