دورية أكاديمية
Apoptosis signal-regulating kinase 1 inhibition in and models of pulmonary hypertension
| العنوان: | Apoptosis signal-regulating kinase 1 inhibition in and models of pulmonary hypertension |
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| المؤلفون: | Kathryn S. Wilson, Hanna Buist, Kornelija Suveizdyte, John T. Liles, Grant R. Budas, Colin Hughes, Margaret R. MacLean, Martin Johnson, Alistair C. Church, Andrew J. Peacock, David J. Welsh |
| المصدر: | Pulmonary Circulation, Vol 10 (2020) |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| المجموعة: | LCC:Diseases of the circulatory (Cardiovascular) system LCC:Diseases of the respiratory system |
| مصطلحات موضوعية: | Diseases of the circulatory (Cardiovascular) system, RC666-701, Diseases of the respiratory system, RC705-779 |
| الوصف: | Pulmonary arterial hypertension, group 1 of the pulmonary hypertension disease family, involves pulmonary vascular remodelling, right ventricular dysfunction and cardiac failure. Oxidative stress, through activation of mitogen-activated protein kinases is implicated in these changes. Inhibition of apoptosis signal-regulating kinase 1, an apical mitogen-activated protein kinase, prevented pulmonary arterial hypertension developing in rodent models. Here, we investigate apoptosis signal-regulating kinase 1 in pulmonary arterial hypertension by examining the impact that its inhibition has on the molecular and cellular signalling in established disease. Apoptosis signal-regulating kinase 1 inhibition was investigated in in vivo pulmonary arterial hypertension and in vitro pulmonary hypertension models. In the in vivo model, male Sprague Dawley rats received a single subcutaneous injection of Sugen SU5416 (20 mg/kg) prior to two weeks of hypobaric hypoxia (380 mmHg) followed by three weeks normoxia (Sugen/hypoxic), then animals were either maintained for three weeks on control chow or one containing apoptosis signal-regulating kinase 1 inhibitor (100 mg/kg/day). Cardiovascular measurements were carried out. In the in vitro model, primary cultures of rat pulmonary artery fibroblasts and rat pulmonary artery smooth muscle cells were maintained in hypoxia (5% O 2 ) and investigated for proliferation, migration and molecular signalling in the presence or absence of apoptosis signal-regulating kinase 1 inhibitor. Sugen/hypoxic animals displayed significant pulmonary arterial hypertension compared to normoxic controls at eight weeks. Apoptosis signal-regulating kinase 1 inhibitor decreased right ventricular systolic pressure to control levels and reduced muscularised vessels in lung tissue. Apoptosis signal-regulating kinase 1 inhibition was found to prevent hypoxia-induced proliferation, migration and cytokine release in rat pulmonary artery fibroblasts and also prevented rat pulmonary artery fibroblast-induced rat pulmonary artery smooth muscle cell migration and proliferation. Apoptosis signal-regulating kinase 1 inhibition reversed pulmonary arterial hypertension in the Sugen/hypoxic rat model. These effects may be a result of intrinsic changes in the signalling of adventitial fibroblast. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-8940 20458940 |
| Relation: | https://doaj.org/toc/2045-8940 |
| DOI: | 10.1177/2045894020922810 |
| URL الوصول: | https://doaj.org/article/6525394d6a864924aa813898fecdb00f |
| رقم الأكسشن: | edsdoj.6525394d6a864924aa813898fecdb00f |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20458940 |
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| DOI: | 10.1177/2045894020922810 |