Effects of BM-573 on Endothelial dependent relaxation and increased blood pressure at early stages of atherosclerosis

Miguel Romero, Elvira Leon-Gomez, Irina Lobysheva, Géraldine Rath, Jean-Michel Dogne, Olivier Feron, Chantal Dessy

Résultats de recherche: Contribution à un journal/une revueArticle

Résumé

Endothelial dysfunction is considered to be an early event in atherosclerosis and plays a pivotal role in the development, progression and clinical complications of atherosclerosis. Previous studies have shown the beneficial effects of combined inhibition of thromboxane synthase and antagonism of thromboxane receptors by BM-573 on atherosclerosis; however our knowledge about the beneficial effects of BM-573 on endothelial function and increased blood pressure related to early stage of atherosclerosis is limited. In the present study, we investigated the effects of short-term (3uM, 1 hour) and chronic (10mg/L, 8 weeks) treatments with BM-573 on vasodilatory function, nitric oxide (NO) bioavailability, oxidative stress and systolic blood pressure in 15 weeks old apolipoprotein E-deficient (ApoE-KO) mice. ApoE-KO mice showed a reduced endothelium-derived relaxation. In addition, NO bioavailability was reduced and oxidative stress and blood pressure were increased in ApoE-KO mice versus wild-type mice. BM-573 treatments were able to improve the relaxation profile in ApoE-KO mice. Short-term effects of BM-573 were mainly mediated by an increased phosphorylation of both eNOS and Akt, whereas BM-573 in vivo treatment also reduced oxidative stress and restored NO bioavailability. In addition, chronic administration of BM-573 reduced systolic blood pressure in ApoE-KO mice. In conclusion, pharmacological modulation of TxA2 biosynthesis and biological activities by dual TP antagonism/TxAS inhibition with BM-573, already known to prevent plaque formation, has the potential to correct vasodilatory dysfunction at the early stages of atherosclerosis.

langueAnglais
Numéro d'articlee0152579
journalPLoS ONE
Volume11
Numéro3
Les DOIs
étatPublié - 1 mars 2016

Empreinte digitale

Blood pressure
atherosclerosis
blood pressure
Atherosclerosis
Apolipoproteins E
Blood Pressure
mice
Oxidative stress
nitric oxide
bioavailability
thromboxanes
oxidative stress
systolic blood pressure
Biological Availability
Nitric Oxide
Oxidative Stress
apolipoprotein E
Thromboxane Receptors
endothelium
Phosphorylation

Citer ceci

Romero, Miguel ; Leon-Gomez, Elvira ; Lobysheva, Irina ; Rath, Géraldine ; Dogne, Jean-Michel ; Feron, Olivier ; Dessy, Chantal. / Effects of BM-573 on Endothelial dependent relaxation and increased blood pressure at early stages of atherosclerosis. Dans: PLoS ONE. 2016 ; Vol 11, Numéro 3.
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Effects of BM-573 on Endothelial dependent relaxation and increased blood pressure at early stages of atherosclerosis. / Romero, Miguel; Leon-Gomez, Elvira; Lobysheva, Irina; Rath, Géraldine; Dogne, Jean-Michel; Feron, Olivier; Dessy, Chantal.

Dans: PLoS ONE, Vol 11, Numéro 3, e0152579, 01.03.2016.

Résultats de recherche: Contribution à un journal/une revueArticle

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AU - Romero,Miguel

AU - Leon-Gomez,Elvira

AU - Lobysheva,Irina

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AU - Dogne,Jean-Michel

AU - Feron,Olivier

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