التفاصيل البيبلوغرافية
| العنوان: |
Inhibition of Soluble Epoxide Hydrolase Does Not Promote or Aggravate Pulmonary Hypertension in Rats |
| المؤلفون: |
Matthieu Leuillier, Valentin Platel, Ly Tu, Guillaume Feugray, Raphaël Thuillet, Déborah Groussard, Hind Messaoudi, Mina Ottaviani, Mustapha Chelgham, Lionel Nicol, Paul Mulder, Marc Humbert, Vincent Richard, Christophe Morisseau, Valéry Brunel, Thomas Duflot, Christophe Guignabert, Jérémy Bellien |
| المصدر: |
Cells; Volume 12; Issue 4; Pages: 665 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2023 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
soluble epoxide hydrolase, epoxyeicosatrienoic acids, pulmonary arterial hypertension, right ventricular dysfunction |
| الوصف: |
Inhibitors of soluble epoxide hydrolase (sEH), which catalyzes the hydrolysis of various natural epoxides to their corresponding diols, present an opportunity for developing oral drugs for a range of human cardiovascular and inflammatory diseases, including, among others, diabetes and neuropathic pain. However, some evidence suggests that their administration may precipitate the development of pulmonary hypertension (PH). We thus evaluated the impact of chronic oral administration of the sEH inhibitor TPPU (N-[1-(1-Oxopropyl)-4-piperidinyl]-N′-[4-(trifluoromethoxy)phenyl]-urea) on hemodynamics, pulmonary vascular reactivity, and remodeling, as well as on right ventricular (RV) dimension and function at baseline and in the Sugen (SU5416) + hypoxia (SuHx) rat model of severe PH. Treatment with TPPU started 5 weeks after SU5416 injection for 3 weeks. No differences regarding the increase in pulmonary vascular resistance, remodeling, and inflammation, nor the abolishment of phenylephrine-induced pulmonary artery constriction, were noted in SuHx rats. In addition, TPPU did not modify the development of RV dysfunction, hypertrophy, and fibrosis in SuHx rats. Similarly, none of these parameters were affected by TPPU in normoxic rats. Complementary in vitro data demonstrated that TPPU reduced the proliferation of cultured human pulmonary artery-smooth muscle cells (PA-SMCs). This study demonstrates that inhibition of sEH does not induce nor aggravate the development of PH and RV dysfunction in SuHx rats. In contrast, a potential beneficial effect against pulmonary artery remodeling in humans is suggested. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| Relation: |
Cellular Pathology; https://dx.doi.org/10.3390/cells12040665 |
| DOI: |
10.3390/cells12040665 |
| الاتاحة: |
https://doi.org/10.3390/cells12040665 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: |
edsbas.DA06FFB6 |
| قاعدة البيانات: |
BASE |