RT Journal Article
T1 FXa inhibition by rivaroxaban modifies mechanisms associated with the pathogenesis of human abdominal aortic aneurysms
A1 Moñux Ducaju, Guillermo
A1 Zamorano León, José Javier
A1 Marqués Pablo, 
A1 Sopeña, Bernardo
A1 García García, José Manuel
A1 Laich de Koller, Guillermo
A1 Calvo Rico, Bibiana
A1 García Fernández, Miguel Ángel
A1 Serrano, Javier
A1 López Farre, Antonio José
AB AimsTo evaluate if rivaroxaban, an oral factor Xa (FXa) inhibitor, could modify the expression in vitro of inflammatory and oxidative stress biomarkers in abdominal aortic aneurysmal (AAA) sites showing intraluminal thrombus.MethodsAAA sites with intraluminal mural thrombus were obtained from six patients undergoing elective AAA repair. In addition, control abdominal aortic samples were obtained from six organ donors. AAA sites were incubated in the presence and absence of 50 nmol l–1 rivaroxaban.ResultsAAA sites showing thrombus demonstrated higher content of FXa than control. Interleukin-6 levels released from AAA [Control: median: 23.45 (interquartile range: 16.17–37.15) vs. AAA: median: 153.07 (interquartile range: 100.80–210.69) pg ml–1 mg tissue–1, P < 0.05] and the expression levels of nitric oxide synthase 2 were significantly higher in AAA than in control. The protein expression level of NADPH oxidase subunits gp67-and gp91-phox, but did not gp47-phox, were also significantly higher in the AAA sites than in control. Addition of rivaroxaban to AAA sites explants significantly reduced the release of interleukin-6 [median: 51.61 (interquartile range: 30.87–74.03) pg ml–1 mg tissue–1, P < 0.05 with respect to AAA alone] and the content of nitric oxide synthase 2, gp67 and gp91-phox NADPH subunits. The content of matrix metallopeptidase 9 was significantly higher in the AAA sites as compared to control. Rivaroxaban also reduced matrix metallopeptidase 9 content in AAA sites to similar levels to control.ConclusionsFXa inhibition by rivaroxaban exerted anti-inflammatory and antioxidative stress properties in human AAA sites, suggesting a role of FXa in these mechanisms associated with the pathogenesis of AAA.
PB Wiley | British Pharmacological Society
SN 0306-5251
YR 2017
FD 2017-07-09
LK https://hdl.handle.net/20.500.14352/99301
UL https://hdl.handle.net/20.500.14352/99301
LA eng
NO Moñux G, Zamorano-León JJ, Marqués P, Sopeña B, García-García JM, Laich de Koller G, Calvo-Rico B, García-Fernandez MA, Serrano J, López-Farré A. FXa inhibition by rivaroxaban modifies mechanisms associated with the pathogenesis of human abdominal aortic aneurysms. Br J Clin Pharmacol. 2017 Dec;83(12):2661-2670. doi: 10.1111/bcp.13383. Epub 2017 Aug 27. PMID: 28735510; PMCID: PMC5698591.
DS Docta Complutense
RD 7 abr 2025