Factor Xa Inhibition by Rivaroxaban Modified Mitochondrial-Associated Proteins in Human Abdominal Aortic Aneurysms
| Autor: | Khaoula Zekri-Nechar, Guillermo Moñux, Antonio Gonzalez-Cantalapiedra, Gala Freixer, Javier Serrano, José J. Zamorano-León, Maday Cabrero-Fernandez, Antonio Segura, Mariano de la Serna-Soto, Antonio López Farré |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male macromolecular substances 030204 cardiovascular system & hematology Mitochondrion Pharmacology 030218 nuclear medicine & medical imaging Mitochondrial Proteins 03 medical and health sciences 0302 clinical medicine Rivaroxaban medicine.artery Mitophagy Humans Medicine Citrate synthase Cytochrome c oxidase Aorta Abdominal cardiovascular diseases Aged Aorta biology business.industry Thrombosis General Medicine Middle Aged Mitochondria Mitochondrial respiratory chain Case-Control Studies cardiovascular system biology.protein Biomarker (medicine) Female Surgery Cardiology and Cardiovascular Medicine business Aortic Aneurysm Abdominal Factor Xa Inhibitors medicine.drug |
| Zdroj: | Annals of Vascular Surgery. 67:482-489 |
| ISSN: | 0890-5096 |
| Popis: | The presence of intraluminal thrombus and mitochondrial dysfunction in human abdominal aortic aneurysms (AAAs) have been associated with aneurysmal growth and rupture. The objective of the study was to study if endogenous factor Xa (FXa) may modulate mitochondrial functionality and expression of proteins associated with mitophagy in human AAAs.AAA sites with intraluminal thrombus were obtained from 6 patients undergoing elective AAA surgery repair. Control samples were collected from 6 organ donors. The effect of FXa was analyzed by in vitro incubation of AAA with 50 nmol/L rivaroxaban, an oral FXa inhibitor.The enzymatic activities of citrate synthase, a biomarker of mitochondrial density, and cytochrome C oxidase, a biomarker of mitochondrial respiratory chain functionality, were significantly reduced in the AAA sites with respect to the healthy aorta (citrate synthase activity in μU/min/μg protein: control: 3.51 ± 0.22 vs. AAA: 0.37 ± 0.15.; P 0.01; cytochrome C oxidase activity in μOD/min/μg protein: control: 8.05 ± 1.57 vs. AAA: 3.29 ± 1.05; P 0.05). The addition of rivaroxaban to AAA reverted the activity of both citrate synthase and cytochrome C oxidase to similar values to control. Mitochondrial Drp-1 expression was higher in AAA sites than in either control aortas or rivaroxaban-incubated AAA sites. Cytosolic content of Drp-1 phosphorylated at Ser637, mitochondrial Parkin, and mitochondrial PINK1-Parkin interaction were significantly reduced in the AAA sites with respect to control aortas. For all these parameters, rivaroxaban-incubated AAA showed similar values compared with control aortas.In human AAA, rivaroxaban improved mitochondrial functionality that was associated with changes in proteins related to mitophagy. Its opens possible new effects of endogenous FXa on the mitochondria in the human AAA site. |
| Databáze: | OpenAIRE |
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