2026-07-23T17:11:54Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/76662024-09-27T10:13:50Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19607
Repisalud
author
Martinez-Pinna, Roxana
author
Madrigal-Matute, Julio
author
Tarín, Carlos
author
Burillo, Elena
author
Esteban-Salan, Margarita
author
Pastor-Vargas, Carlos
author
Lindholt, Jes S
author
Lopez, Juan Antonio
author
Calvo, Enrique
author
de Ceniga, Melina Vega
author
Meilhac, Olivier
author
Egido, Jesus
author
Blanco-Colio, Luis M
author
Michel, Jean-Baptiste
author
Martin-Ventura, Jose L
funder
European Commission
funder
Ministerio de Ciencia e Innovación (España)
funder
Ministerio de Sanidad y Consumo (España)
funder
Instituto de Salud Carlos III
funder
Fundación ProCNIC
funder
Fundación Lilly
2019-05-23T12:21:02Z
2019-05-23T12:21:02Z
2013-08
Arterioscler Thromb Vasc Biol. 2013; 33(8):2013-20
10.1161/ATVBAHA.112.301191
1524-4636
1079-5642
Arteriosclerosis, thrombosis, and vascular biology
23702661
http://hdl.handle.net/20.500.12105/7666
OBJECTIVE: To identify proteins related to intraluminal thrombus biological activities that could help to find novel pathological mechanisms and therapeutic targets for human abdominal aortic aneurysm (AAA). APPROACH AND RESULTS: Tissue-conditioned media from patients with AAA were analyzed by a mass spectrometry-based strategy using liquid chromatography coupled to tandem mass spectrometry. Global pathway analysis by Ingenuity software highlighted the presence of several circulating proteins, among them were proteins from the complement system. Complement C3 concentration and activation were assessed in plasma from AAA patients (small AAA, AAA diameter=3-5 cm and large AAA, AAA diameter >5 cm), showing decreased C3 levels and activation in large AAA patients. No association of a combination of single-nucleotide polymorphisms in complement genes between large and small AAA patients was observed. Intense extracellular C3 inmunostaining, along with C9, was observed in AAA thrombus. Analysis of C3 in AAA tissue homogenates and tissue-conditioned media showed increased levels of C3 in AAA thrombus, as well as proteolytic fragments (C3a/C3c/C3dg), suggesting its local deposition and activation. Finally, the functional role of local complement activation in polymorphonuclear (PMN) cell activation was tested, showing that C3 blockade by anti-C3 antibody was able to decrease thrombus-induced neutrophil chemotaxis and reactive oxygen species production. CONCLUSIONS: A decrease of systemic C3 concentration and activity in the later stages of AAA associated with local complement retention, consumption, and proteolysis in the thrombus could induce PMN chemotaxis and activation, playing a detrimental role in AAA progression.
eng
Aortic aneurysm, abdominal
Complement system proteins
Inflammation
Neutrophils
Thrombosis
Proteomic analysis of intraluminal thrombus highlights complement activation in human abdominal aortic aneurysms
journal article
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