ArticleJournal of the American Heart Association2019
Rivaroxaban, a Direct Factor Xa Inhibitor, Ameliorates Hypertensive Renal Damage Through Inhibition of the Inflammatory Response Mediated by Protease-Activated Receptor Pathway.
Article in Journal of the American Heart Association, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 42 citations in OpenAlex.
- Switching from Warfarin to rivaroxaban induces sufficiency of vitamin K and reduction of arterial stiffness in patients with atrial fibrillation.Heart and vessels · 2020Trial
- Effect of rivaroxaban on urinary albumin excretion in patients with atrial fibrillation and chronic kidney disease: a randomized trial (X-NOAC).Hypertension research : official journal of the Japanese Society of Hypertension · 2020Trial
- Rivaroxaban suppresses factor Xa-Driven PAR-2-ERK inflammatory, catabolic, osteoclastogenic, and mitochondrial dysfunction signaling in osteoarthritis-relevant chondrocytes: a drug-repurposing strategy for joint inflammation.Frontiers in pharmacology · 2026Article
- Anticoagulation in Chronic Kidney Disease.Drugs · 2024Review
- Comparative Cardioprotective Effectiveness: NOACs vs. Nattokinase-Bridging Basic Research to Clinical Findings.Biomolecules · 2024Review
- Inhibitory effect of rivaroxaban on protease-activated receptor-2 in circulating neutrophils among patients with atrial fibrillation.International journal of cardiology. Heart & vasculature · 2024Article
- Evaluating Renal Benefits of Rivaroxaban Versus Vitamin K Antagonists in Atrial Fibrillation: A Systematic Review and Meta-analysis of Real-world Evidence.European cardiology · 2024Review
- The role of coagulome in the tumor immune microenvironment.Advanced drug delivery reviews · 2023Review
- Novel Isosteviol-Based FXa Inhibitors: Molecular Modeling, In Silico Design and Docking Simulation.Molecules (Basel, Switzerland) · 2023Article
- The effectiveness of atorvastatin for the prevention of deep vein thrombosis in cancer patients undergoing chemotherapy : A randomised controlled trial: open label.Thrombosis journal · 2023Article
- Pathophysiological Role of Microglial Activation Induced by Blood-Borne Proteins in Alzheimer's Disease.Biomedicines · 2023Review
- The effect of rivaroxaban on biomarkers in blood and plasma: a review of preclinical and clinical evidence.Journal of thrombosis and thrombolysis · 2023Review
- Direct oral anticoagulant agents attenuate temporary aortic occlusion-induced renal oxidative and inflammatory responses in rats.Turk gogus kalp damar cerrahisi dergisi · 2022Article
- Control of hippocampal prothrombin kringle-2 (pKr-2) expression reduces neurotoxic symptoms in five familial Alzheimer's disease mice.British journal of pharmacology · 2022Article
- Cardioprotection by direct factor Xa inhibition in angiotensin II overexpression.Hypertension research : official journal of the Japanese Society of Hypertension · 2021Article
- Rivaroxaban attenuates cardiac hypertrophy by inhibiting protease-activated receptor-2 signaling in renin-overexpressing hypertensive mice.Hypertension research : official journal of the Japanese Society of Hypertension · 2021Article
- Interplay between inflammation and thrombosis in cardiovascular pathology.Nature reviews. Cardiology · 2021Review
- Novel Targets for Hypertension Drug Discovery.Current hypertension reports · 2021Review
- Non-valvular Atrial Fibrillation in CKD: Role of Vitamin K Antagonists and Direct Oral Anticoagulants. A Narrative Review.Frontiers in medicine · 2021Review
- Blockade of PAR-1 Signaling Attenuates Cardiac Hypertrophy and Fibrosis in Renin-Overexpressing Hypertensive Mice.Journal of the American Heart Association · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background An enhanced renin-angiotensin system causes hypertensive renal damage. Factor Xa not only functions in the coagulation cascade but also activates intracellular signaling through protease-activated receptors ( PAR ). We investigated the effects of rivaroxaban, a factor Xa inhibitor, on hypertensive renal damage in hypertensive mice overexpressing renin (Ren-TG). Methods and Results The 12- to 16-week-old Ren-TG and wild-type mice were orally administered with or without 6 or 12 mg/kg of rivaroxaban for 1 or 4 months. Plasma factor Xa was significantly increased in the Ren-TG compared with the wild-type mice and was reduced by 12 mg/kg of rivaroxaban ( P<0.05). Urinary albumin excretion (UAE) was higher in the nontreated 8-month-old Ren-TG than in the wild-type mice (69.6±29 versus 20.1±8.2 μg/day; P<0.01). Treatment with 12 mg/kg of rivaroxaban for 4 months decreased the UAE to 38.1±13.2 μg/day ( P<0.01). Moreover, rivaroxaban treatment attenuated histologic changes of glomerular hypertrophy, mesangial matrix expansion, effacement of the podocyte foot process, and thickened glomerular basement membrane in the Ren-TG. The renal expression of PAR -2 was increased in the Ren-TG, but was inhibited with rivaroxaban treatment. In vitro study using the human podocytes showed that the expressions of PAR -2 and inflammatory genes and nuclear factor--κB activation were induced by angiotensin II stimulation, but were inhibited by rivaroxaban. PAR -2 knockdown by small interfering RNA also attenuated the PAR -2-related inflammatory gene expressions. Conclusions These findings indicate that rivaroxaban exerts protective effects against angiotensin II-induced renal damage, partly through inhibition of the PAR -2 signaling-mediated inflammatory response.
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