1. Association of ficolin-3 with abdominal aortic aneurysm presence and progression
- Author
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Peter Garred, Luis Miguel Blanco-Colio, Carla Mazzeo, Katrine Pilely, Jesús Egido, Elena Burillo, Diego Martinez-Lopez, Jean-Baptiste Michel, José Luis Martín-Ventura, Carlos-Ernesto Fernandez-García, and Jes S. Lindholt
- Subjects
0301 basic medicine ,Male ,Pathology ,blood platelets ,Denmark ,complement system proteins ,030204 cardiovascular system & hematology ,Aortic aneurysm ,0302 clinical medicine ,Aortic Aneurysm, Abdominal/blood ,Lectins ,Mass Screening ,Platelet ,Hematology ,Middle Aged ,Abdominal aortic aneurysm ,Peripheral Arterial Disease/diagnosis ,Hypertension/diagnosis ,Hypertension ,cardiovascular system ,Disease Progression ,Biomarker (medicine) ,Blood Platelets/metabolism ,medicine.symptom ,biological markers ,aortic aneurysm, abdominal ,Blood Platelets ,medicine.medical_specialty ,Culture Media, Conditioned/chemistry ,cell-derived microparticles ,exosomes ,macromolecular substances ,Biology ,Asymptomatic ,03 medical and health sciences ,Peripheral Arterial Disease ,medicine ,Lectins/blood ,Humans ,cardiovascular diseases ,Platelet activation ,Thrombus ,Glycoproteins/blood ,Aged ,Glycoproteins ,Microcirculation ,medicine.disease ,Microvesicles ,030104 developmental biology ,Culture Media, Conditioned ,Biomarkers/blood ,Biomarkers ,Aortic Aneurysm, Abdominal - 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. SummaryBackground 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.
- Published
- 2016