Sphingosine Kinase 1 Deficiency Protects Rodents From Chronic Hypoxia-Mediated Pulmonary Hypertension
| Autor: | Krystina M. Shioura, Garcia Jgn, Chen Jw, Jiwang Chen, Srikanth Pendyala, Jason X.-J. Yuan, L. Huan, Roberto F. Machado, Joe G.N. Garcia, Shioura Km, Saad Sammani, Machado Rf, Liliana Moreno-Vinasco, Vijay Mohan, Long Shuang Huang, Viswanathan Natarajan |
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| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Sphingosine biology Kinase business.industry medicine.disease Pulmonary hypertension Muscle hypertrophy chemistry.chemical_compound Endocrinology medicine.anatomical_structure chemistry Sphingosine kinase 1 Right ventricular hypertrophy Ventricle Internal medicine medicine Ventricular pressure biology.protein business |
| Zdroj: | B63. EXPERIMENTAL MODELS IN PULMONARY HYPERTENSION I. |
| DOI: | 10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a3440 |
| Popis: | Rationale: Sphingosine kinases (SphKs) 1 and 2 regulate the synthesis of the bioactive sphingolipid sphingosine 1-phosphate (S1P), an important lipid mediator that promotes endothelial cell proliferation, migration and angiogenesis. We hypothesized that SphK1 deficiency protects against the development of pulmonary hypertension (PH). Methods: SphK1-deficient mice (SphK1KO) and C57Bl6 wild-type littermates (WT) were exposed to normoxia or 10% FiO for four weeks 2 (n= 6-8 per group). Adult male Dahl salt-sensitive (SS) rats (250–300 g, n= 6 per group) were exposed to normoxia or 10% FiO for 3.5 weeks 2 and received SphK inhibitor (SphKI2, Cayman, 10mg/kg body weight) or diluent every other day for 3.5 weeks. Right ventricular systolic pressure (RVSP) was determined with a pressure transducer catheter. The right ventricle: left ventricle +septum (RV/LV+S) ratio was calculated. Results: Under normoxia RVSP and RV/LV+S did not differ between SphK1KO and WT mice. After four-weeks of hypoxic exposure, SphK1KO mice developed significantly less severe PH (RVSP 30.09±0.68 36.77±1.07 mmHg, , Figure A) and right ventricular vs. p |
| Databáze: | OpenAIRE |
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