2026-07-23T17:11:51Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/76662024-09-27T10:13:50Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19607

00925njm 22002777a 4500 dc 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 author 2013-08 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. 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 Aortic aneurysm, abdominal Complement system proteins Inflammation Neutrophils Thrombosis Proteomic analysis of intraluminal thrombus highlights complement activation in human abdominal aortic aneurysms