期刊
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
卷 15, 期 3, 页码 575-585出版社
WILEY
DOI: 10.1111/jth.13608
关键词
aortic aneurysm; abdominal; biological markers; blood platelets; cell-derived microparticles; complement system proteins; exosomes
资金
- Spanish MICIN [SAF2013/42525, SAF2016-80843-R]
- Fondo de Investigaciones Sanitarias ISCiii-FEDER (Biobancos) [RD09/0076/00101]
- Centro de Investigacion Biomedica en Red de Enfermedades cardiovasculares (CIBERCV)
- Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM)
- FRIAT
- Novo Nordic Research Foundation
- Research Foundation of the Danish Heart Association
- Research Foundation of Rigshospitalet
- Svend Andersen Research Foundation
- Novo Nordisk Fonden [NNF13SA0009309] Funding Source: researchfish
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.
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