FXa inhibition by rivaroxaban modifies mechanisms associated with the pathogenesis of human abdominal aortic aneurysms

Moñux, Guillermo; Zamorano-León, José J.; Marques, Pedro Rocha; Sopeña, B.; García-García, José Manuel; Koller, Gabriele; Calvo-Rico, Bibiana; Garcı́a-Fernández, Miguel Ángel; Serrano, Javier; López‐Farré, Antonio

doi:10.1111/bcp.13383

Cited by 31 publications

(38 citation statements)

References 51 publications

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“…The gels were blotted onto nitrocellulose (NC) membranes. As previously reported (Zamorano-León et al, 2013; Moñux et al, 2017), NC membranes were blocked with 5% (w/v) bovine serum albumin (BSA) and incubated with monoclonal antibodies against Mfn-1 (1:2,000, sc-166644, Santa Cruz Biotechnology, Inc., Santa Cruz, CA, USA), Mfn-2 (1:1,000, sc-2031, Santa Cruz Biotechnology, Inc.), Drp-1 (1:750, Ab56788, Abcam, Cambridge, UK), and B-cell lymphoma 2 (Bcl-2)-antagonist/killer (Bak) (1:1,000, Ab32371, Abcam), and polyclonal antibodies against p53 (1:1,000, sc-6243, Santa Cruz Biotechnology, Inc.), cyclin B1 (1:1,500, Ab2949, Abcam), Bcl-2-associated X protein (Bax) (1:1,000, sc-493, Santa Cruz Biotechnology, Inc.), and Bcl-2 (1:1,000, sc-783, Santa Cruz Biotechnology, Inc.). A monoclonal anti-β-actin antibody (1:7,500, A-5441, Sigma-Aldrich Co.) was used as a control for protein loading.…”

Section: Methodssupporting

confidence: 85%

“…Protein expression was determined by Western blotting. In brief, and as we have previously reported (Zamorano-León et al, 2013; Moñux et al, 2017), protein concentrations were estimated using the bicinchoninic acid reagent (Thermo Fisher Scientific, Inc., Waltham, MA, USA), and equal amount (40 μg/lane) of each lysate were loaded onto denaturing sodium dodecyl sulphate-polyacrylamide gel electrophoresis 15% (w/v) polyacrylamide gels. The gels were blotted onto nitrocellulose (NC) membranes.…”

Section: Methodsmentioning

confidence: 99%

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Effect of Pectin on the Expression of Proteins Associated with Mitochondrial Biogenesis and Cell Senescence in HT29-Human Colorectal Adenocarcinoma Cells

Zamorano-León

Ballesteros

Heras

et al. 2019

pnf

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Mitochondria dynamic is regulated by different proteins, maintaining a balance between fission and fusion. An imbalance towards mitochondrial fission has been associated with tumor cell proliferation. The aim of this study was to analyze whether pectin modifies the viability of human colon cancer cells and the expression of proteins involved in mitochondrial fusion and fission. The human colon carcinoma cell line HT29 cells was growth in 10% fetal bovine serum in the absence and presence of pectin. Pectin reduced HT29 cell viability in a concentration-dependent manner, reaching a plateau at 150~300 μmol/L pectin. The presence of 200 μmol/L pectin reduced the expression of dynamin-related protein-1 and increased expression of the mitochondrial fusion-associated proteins mitofusin-1 and 2. Expression of cyclin B1, a protein involved in G2/M transition, was found decreased in pectin-incubated HT29 cells. Moreover, expression of p53 protein, the amount of p53 in the nucleous and β-galactosidase activity, which are all biomarkers for cellular senescence, were significantly higher in pectin-incubated HT29 cells than in HT29 cells incubated without pectin. Expression of the protein B-cell lymphoma 2 (Bcl-2) homologous antagonist/killer was increased in response to incubation with pectin. However, incubation with pectin did not affect expression of Bcl-2-associated X protein or Bcl-2, or the caspase-3 activity. Overall, we concluded that pectin reduces the viability of human HT29 colon cancer cells, which is accompanied with a shift in the expression of proteins associated with mitochondrial dynamics towards mitochondrial fusion. Moreover, incubation with pectin favors cellular senescence over apoptosis in HT29 cells.

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Section: Methodssupporting

confidence: 85%

Section: Methodsmentioning

confidence: 99%

Effect of Pectin on the Expression of Proteins Associated with Mitochondrial Biogenesis and Cell Senescence in HT29-Human Colorectal Adenocarcinoma Cells

Zamorano-León

Ballesteros

Heras

et al. 2019

pnf

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“…These findings indicate a probable role for FXa in the pathogenesis of aneurysms. Perhaps, a better understanding of the role of FXa in aneurysms in the future may create new opportunities and possibilities for the use of direct FXa inhibitors [12].…”

Section: Discussionmentioning

confidence: 99%

Conservative treatment of giant popliteal aneurysm with edoxaban in an elderly man

Fazio,

Alcamo,

Schirò

2020

J. Mol. Clin. Med.

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Although popliteal aneurysm is an uncommon condition, it is the most common peripheral artery aneurysm. Peripheral artery aneurysms may dilate or rupture, but can also result in embolism and thrombosis. The optimal management strategy for unoperated popliteal aneurysm and the prophylaxis of thromboembolism in high-risk patients remains to be determined. We present the case of an 81-year-old man with an unoperated popliteal aneurysm with a maximum diameter of 55 mm that was conservatively treated with direct oral anticoagulation and periodic surveillance. The patient also had Alzheimer's disease and other severe comorbidities. He refused surgery; therefore, we decided to treat him with 30 mg of edoxaban daily to reduce the risk of thrombosis and distal embolism. The patient was followed up with a medical examination and ultrasound monitoring every six months. After a 5-years of follow-up, the size of the aneurysm remained stable, and there were no episodes of thrombosis or limb embolism. No bleeding or adverse effects were reported. These results suggest that a conservative approach with direct oral anticoagulation and periodic surveillance might be an effective strategy for patients at high surgical risk, with limited life expectancy or who refuse operative repair. However, further research and evidence are needed to support direct oral anticoagulation for conservative popliteal aneurysm treatment.

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“…Activated MMP-9 in particularly is thought to be both cause and biomarker of fibrotic remodeling predisposing to arrhythmias [66][67][68][69]. Thrombin and FXa both regulate MMP-9 expression and activity [70][71][72][73][74][75] while DOAC treatment reduces MMP-9 levels [76][77][78], which may be one means by which DOAC could limit the structural changes that support AF maintenance. Fibrotically remodeled atrial tissue is characterized by excess collagen that compromises impulse propagation that supports arrhythmia development [79][80][81].…”

Section: Inhibition Of the Fibro-inflammatory Substrate Supporting Afmentioning

confidence: 99%

Straight to the heart: Pleiotropic antiarrhythmic actions of oral anticoagulants

Fender

Wakili

Dobrev

2019

Pharmacological Research

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Mechanistic understanding of atrial fibrillation (AF) pathophysiology and the complex bidirectional relationship with thromboembolic risk remains limited. Oral anticoagulation is a mainstay of AF management. An emerging concept is that anticoagulants may themselves have potential pleiotropic disease-modifying effects. We here review the available evidence for hemostasis-independent actions of the oral anticoagulants on electrical and structural remodeling, and the inflammatory component of the vulnerable substrate.

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FXa inhibition by rivaroxaban modifies mechanisms associated with the pathogenesis of human abdominal aortic aneurysms

Abstract: 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.

Cited by 31 publications

References 51 publications

Effect of Pectin on the Expression of Proteins Associated with Mitochondrial Biogenesis and Cell Senescence in HT29-Human Colorectal Adenocarcinoma Cells

Effect of Pectin on the Expression of Proteins Associated with Mitochondrial Biogenesis and Cell Senescence in HT29-Human Colorectal Adenocarcinoma Cells

Conservative treatment of giant popliteal aneurysm with edoxaban in an elderly man

Straight to the heart: Pleiotropic antiarrhythmic actions of oral anticoagulants

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