Rivaroxaban attenuates cardiac hypertrophy by inhibiting protease-activated receptor-2 signaling in renin-overexpressing hypertensive mice
| العنوان: | Rivaroxaban attenuates cardiac hypertrophy by inhibiting protease-activated receptor-2 signaling in renin-overexpressing hypertensive mice |
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| المؤلفون: | Shuntaro Sakai, Maiko Senoo, Tomohiro Osanai, Hirofumi Tomita, Noritomo Narita, Kenji Hanada, Ken Okumura, Yosuke Kawamura, Hiroaki Ichikawa, Yoshikazu Yokono, Masato Narita, Michiko Shimada |
| المصدر: | Hypertension Research. 44:1261-1273 |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, Physiology, Cardiac fibrosis, Cardiomegaly, Mice, Rivaroxaban, Fibrosis, Internal medicine, Renin, Renin–angiotensin system, Internal Medicine, medicine, Animals, Receptor, PAR-2, Protease-activated receptor, Receptor, Protease-activated receptor 2, business.industry, Myocardium, medicine.disease, Endocrinology, Tumor necrosis factor alpha, Cardiology and Cardiovascular Medicine, business, Factor Xa Inhibitors, Transforming growth factor |
| الوصف: | Rivaroxaban (Riv), a direct factor Xa (FXa) inhibitor, exerts anti-inflammatory effects in addition to anticoagulation. However, its role in cardiovascular remodeling is largely unknown. We tested the hypothesis that Riv attenuates the progression of cardiac hypertrophy and fibrosis induced by continuous activation of the renin-angiotensin system (RAS) in renin-overexpressing hypertensive transgenic (Ren-Tg) mice. We treated 12-week-old male Ren-Tg and wild-type (WT) mice with a diet containing Riv (12 mg/kg/day) or a regular diet for 4 weeks. After this, FXa in plasma significantly increased in Ren-Tg mice compared with WT mice, and Riv inhibited this increase. Left ventricular wall thickness (LVWT) and the area of cardiac fibrosis evaluated by Masson's trichrome staining were greater in Ren-Tg mice than in WT mice, and Riv decreased them. Cardiac expression levels of the protease-activated receptor (PAR)-2, tumor necrosis factor-α, transforming growth factor (TGF)-β1, and collagen type 3 α1 (COL3A1) genes were all greater in Ren-Tg mice than in WT mice, and Riv attenuated these increases. To investigate the possible involvement of PAR-2, we treated Ren-Tg mice with a continuous subcutaneous infusion of 10 μg/kg/day of the PAR-2 antagonist FSLLRY for 4 weeks. FSLLRY significantly decreased LVWT and cardiac expression of PAR-2, TGF-β1, and COL3A1. In isolated cardiac fibroblasts (CFs), Riv or FSLLRY pretreatment inhibited the FXa-induced increase in the phosphorylation of extracellular signal-regulated kinases. In addition, Riv or FSLLRY inhibited FXa-stimulated wound closure in CFs. Riv exerts a protective effect against cardiac hypertrophy and fibrosis development induced by continuous activation of the RAS, partly by inhibiting PAR-2. |
| تدمد: | 1348-4214 0916-9636 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::30fdbf762698147ef2e9912fdff7e601 https://doi.org/10.1038/s41440-021-00700-7 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....30fdbf762698147ef2e9912fdff7e601 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 13484214 09169636 |
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