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00925njm 22002777a 4500 dc Moñux Ducaju, Guillermo author Zamorano León, José Javier author Marqués Pablo author Sopeña, Bernardo author García García, José Manuel author Laich de Koller, Guillermo author Calvo Rico, Bibiana author García Fernández, Miguel Ángel author Serrano, Javier author López Farre, Antonio José author 2017-07-09 Aims To 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. Methods AAA 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. Results AAA 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. Conclusions FXa 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. 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. 0306-5251 10.1111/BCP.13383 https://hdl.handle.net/20.500.14352/99301 https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.13383 28735510 https://pubmed.ncbi.nlm.nih.gov/28735510/ FXa inhibition by rivaroxaban modifies mechanisms associated with the pathogenesis of human abdominal aortic aneurysms