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.

Rivaroxaban versus warfarin: differential effects on oxidative stress and fibrinolytic markers in atrial fibrillation

“…Although the present study found no significant reduction in oxidative stress as measured by TBARS levels, a distinct antioxidant effect of rivaroxaban was observed, evidenced by increased cell viability in the MTT assay. This finding aligns with research by Ishibashi et al and Moñux et al, who reported that FXa inhibition with rivaroxaban downregulates oxidative stress-related proteins and promotes an antioxidant milieu in models of abdominal aortic aneurysm ( Ishibashi et al, 2014 ; Moñux et al, 2017 ). A comparable antioxidant effect has also been documented for edoxaban, another direct FXa inhibitor ( Narita et al, 2019 ).…”

“…Emerging evidence suggests that FXa inhibition by rivaroxaban may attenuate the generation of reactive oxygen species (ROS) through indirect mechanisms ( Woźniak et al, 2020 ; Ishibashi et al, 2014 ; Moñux et al, 2017 ). Supporting this, Woźniak et al demonstrated that rivaroxaban and dabigatran confer protective effects on vascular endothelial cells by reducing ROS production and mitigating DNA damage ( Woźniak et al, 2020 ).…”

Rivaroxaban versus warfarin: differential effects on oxidative stress and fibrinolytic markers in atrial fibrillation

“…Although the present study found no significant reduction in oxidative stress as measured by TBARS levels, a distinct antioxidant effect of rivaroxaban was observed, evidenced by increased cell viability in the MTT assay. This finding aligns with research by Ishibashi et al and Moñux et al, who reported that FXa inhibition with rivaroxaban downregulates oxidative stress-related proteins and promotes an antioxidant milieu in models of abdominal aortic aneurysm ( Ishibashi et al, 2014 ; Moñux et al, 2017 ). A comparable antioxidant effect has also been documented for edoxaban, another direct FXa inhibitor ( Narita et al, 2019 ).…”

“…Emerging evidence suggests that FXa inhibition by rivaroxaban may attenuate the generation of reactive oxygen species (ROS) through indirect mechanisms ( Woźniak et al, 2020 ; Ishibashi et al, 2014 ; Moñux et al, 2017 ). Supporting this, Woźniak et al demonstrated that rivaroxaban and dabigatran confer protective effects on vascular endothelial cells by reducing ROS production and mitigating DNA damage ( Woźniak et al, 2020 ).…”

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

“…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.…”

The elevated expression of TLR4 and MMP9 in human abdominal aortic aneurysm tissues and its implication

“…Because of its capacity to degrade multiple components of ECM, MMP9 has been shown to participate in an important mechanism in the formation and expansion of AAA [ 11 , 12 , 32 ]. There were supporting data that the content of MMP9 was significantly increased in the aortic wall of AAA and MMP9 staining was positive for inflammatory cells and vascular‑related cells [ 15 , 33 , 34 ].…”

Rivaroxaban versus warfarin: differential effects on oxidative stress and fibrinolytic markers in atrial fibrillation

“…Although the present study found no significant reduction in oxidative stress as measured by TBARS levels, a distinct antioxidant effect of rivaroxaban was observed, evidenced by increased cell viability in the MTT assay. This finding aligns with research by Ishibashi et al and Moñux et al, who reported that FXa inhibition with rivaroxaban downregulates oxidative stress-related proteins and promotes an antioxidant milieu in models of abdominal aortic aneurysm ( Ishibashi et al, 2014 ; Moñux et al, 2017 ). A comparable antioxidant effect has also been documented for edoxaban, another direct FXa inhibitor ( Narita et al, 2019 ).…”

“…Emerging evidence suggests that FXa inhibition by rivaroxaban may attenuate the generation of reactive oxygen species (ROS) through indirect mechanisms ( Woźniak et al, 2020 ; Ishibashi et al, 2014 ; Moñux et al, 2017 ). Supporting this, Woźniak et al demonstrated that rivaroxaban and dabigatran confer protective effects on vascular endothelial cells by reducing ROS production and mitigating DNA damage ( Woźniak et al, 2020 ).…”

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

“…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.…”

The elevated expression of TLR4 and MMP9 in human abdominal aortic aneurysm tissues and its implication

“…Because of its capacity to degrade multiple components of ECM, MMP9 has been shown to participate in an important mechanism in the formation and expansion of AAA [ 11 , 12 , 32 ]. There were supporting data that the content of MMP9 was significantly increased in the aortic wall of AAA and MMP9 staining was positive for inflammatory cells and vascular‑related cells [ 15 , 33 , 34 ].…”

Rivaroxaban versus warfarin: differential effects on oxidative stress and fibrinolytic markers in atrial fibrillation

“…Although the present study found no significant reduction in oxidative stress as measured by TBARS levels, a distinct antioxidant effect of rivaroxaban was observed, evidenced by increased cell viability in the MTT assay. This finding aligns with research by Ishibashi et al and Moñux et al, who reported that FXa inhibition with rivaroxaban downregulates oxidative stress-related proteins and promotes an antioxidant milieu in models of abdominal aortic aneurysm ( Ishibashi et al, 2014 ; Moñux et al, 2017 ). A comparable antioxidant effect has also been documented for edoxaban, another direct FXa inhibitor ( Narita et al, 2019 ).…”

“…Emerging evidence suggests that FXa inhibition by rivaroxaban may attenuate the generation of reactive oxygen species (ROS) through indirect mechanisms ( Woźniak et al, 2020 ; Ishibashi et al, 2014 ; Moñux et al, 2017 ). Supporting this, Woźniak et al demonstrated that rivaroxaban and dabigatran confer protective effects on vascular endothelial cells by reducing ROS production and mitigating DNA damage ( Woźniak et al, 2020 ).…”

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

“…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.…”

The elevated expression of TLR4 and MMP9 in human abdominal aortic aneurysm tissues and its implication

“…Because of its capacity to degrade multiple components of ECM, MMP9 has been shown to participate in an important mechanism in the formation and expansion of AAA [ 11 , 12 , 32 ]. There were supporting data that the content of MMP9 was significantly increased in the aortic wall of AAA and MMP9 staining was positive for inflammatory cells and vascular‑related cells [ 15 , 33 , 34 ].…”