Academic Journal
Obesity and Cardiac Microvascular Function
| العنوان: | Obesity and Cardiac Microvascular Function |
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| المؤلفون: | Osto, E, Doytcheva, P, Baechler, T, Tarasco, E, Pellegrini, G, Matter, C, Lutz, T, Luescher, T, Planavila, A, Ruperez, C, Lerin, C, Mas-Stachurska, A, Sitges, M, Giralt, M, Villarroya, F, Huisamen, B, Van Vuuren, M, Espach, Y, Marais, E, Lochner, A |
| بيانات النشر: | Oxford University Press |
| سنة النشر: | 2016 |
| المجموعة: | HighWire Press (Stanford University) |
| مصطلحات موضوعية: | Sunday 10 July 2016 |
| الوصف: | Introduction: Roux-en-Y gastric bypass (RYGB) reduces weight and long-term cardiovascular risk in obese patients. We showed that endothelial-mediated vasorelaxation improves rapidly in diet-induced obese (DIO) rats within 8 days after RYGB and is associated with reduced activation of JNK independently from weight loss. Purpose: We investigated whether in vivo inhibition of JNK with two different JNK inhibitors in sham-operated rats mimics the beneficial endothelial effects of RYGB. Methods: DIO rats underwent RYGB or sham surgery, and sham-operated ad libitum-fed rats received either vehicle (AL) or the unspecific JNK inhibitor SP600125 40mg/kg/day s.c. (SP) for 8 days post-surgery. In a second experiment, sham-operated rats received either control peptide TAT (TAT) or the highly specific JNK peptide inhibitor D-JNKi-1 20mg/kg/day s.c. (DJNK) for 8 days post-surgery. Thereafter, thoracic aortic rings were isolated and subjected to ex vivo isometric tension recordings. After submaximal contraction with norepinephrine (10-6mol/L), cumulative relaxation responses were performed to GLP-1 (7–36) amide (10-12 to 10-6mol/L) or insulin (10-11 to 10-5mol/L). In TAT and DJNK rats, some aortic rings were isolated as before and pre-incubated ex vivo with 5 uM DJNK for 30 min before vasodilation experiments. Western blot analyses of JNK, the inhibitory phosphorylation of insulin receptor substrate-1 (IRS-1) on ser307, and downstream cellular insulin signaling including Akt, eNOS-ser1177 activatory phosphorylation and eNOS dimerization were performed on aortic tissue lysates. Results: GLP-1- and insulin-induced vasodilation improved in RYGB and tended to improve in SP compared to AL rats. The specific JNK inhibitor DJNK completely mimicked the beneficial effects of RYGB surgery on endothelial function 8 days after surgery. Ex vivo aortic pre-incubation with DJNK improved the vascular relaxation of TAT rats, but did not further ameliorate the already restored vasodilation of rats receiving the in vivo DJNK treatment. Aortic ... |
| نوع الوثيقة: | text |
| وصف الملف: | text/html |
| اللغة: | English |
| Relation: | http://cardiovascres.oxfordjournals.org/cgi/content/short/111/suppl_1/S88; http://dx.doi.org/10.1093/cvr/cvw147 |
| DOI: | 10.1093/cvr/cvw147 |
| الاتاحة: | http://cardiovascres.oxfordjournals.org/cgi/content/short/111/suppl_1/S88 https://doi.org/10.1093/cvr/cvw147 |
| Rights: | Copyright (C) 2016, European Society of Cardiology |
| رقم الانضمام: | edsbas.DF166616 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/cvr/cvw147 |
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