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2014 Combined Annual Meeting Abstracts

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CARDIOLOGY/CARDIOVASCULAR DISEASE

FINAL ID: 2 PROMOTERS OF SPHINGOSINE 1-PHOSPHATE RECEPTORS ARE DIFFERENTIALLY REGULATED BY GROWTH FACTORS AND HYPOXIA

X. Sun, B. Liu, J. Sysol, V. Natarajan, J.G. Garcia, R.F. Machado, Medicine, University of Illinois, Chicago, Illinois, UNITED STATES, V. Natarajan Pharmacology, University of Illinois, Chicago, Illinois, UNITED STATES, J.G. Garcia Medicine, University of Arizona, Tucson, Arizona

Rationale: Endothelial dysfunction plays critical a critical role in pulmonary arterial hypertension (PAH). We and others have previously demonstrated that sphingosine 1-phosphate (S1P) and its receptors, S1PR1, S1PR2 and S1PR3, are intimately involved in lung vascular proliferation and endothelial function.

Objective: To explore the transcription regulation of S1PR1, S1PR2 and S1PR3 by hypoxia and growth factors.

Methods: In silico analysis of three S1PR promoters and identification of cis- regulatory elements by TRANSFAC and JASPAR was performed. S1PR1, S1PR2 and S1PR3 promoters were constructed into a luciferase reporter vector in transfected human pulmonary artery endothelial cells (PAECs), stimulated by growth factors VEGF, PDGF, HGF or hypoxia (2% oxygen) for 24 hours. The promoter activities were assessed for functionality by luciferase assay.

Results: Results: In silico analysis of three S1PR promoters identified several putative cis regulatory elements, including binding sites for growth factor induced transcription factors and hypoxia inducible factor. In PAECs, basic promoter activity of S1PR1 was higher than S1PR3 and S1PR2. Promoter activity of S1PR1 was significantly increased by VEGF, PDEF and HGF (p<0.05). Promoter activity of S1PR2 was significantly increased by PDGF, HGF and hypoxia (p<0.05). Promoter activity of S1PR3 was significantly increased by VEGF and PDGF only (p<0.05).

Conclusion: These data suggest that S1P receptors are differentially regulated by growth factors and hypoxia. We speculate that S1PR1, S1PR2 and S1PR3 may play distinct roles in pulmonary vascular remodeling.

FINAL ID: 6 OVER-EXPRESSION OF TNNI3K, A CARDIAC SPECIFIC KINASE, EXACERBATES INFLAMMATION IN COXSACKIEVIRUS B3 (CVB3) MEDIATED VIRAL MYOCARDITIS

S. Parikh, T. Force, Center for Translational Medicine, Temple Medical University, Philadelphia, Pennsylvania, UNITED STATES, A. Bucek D. Fairweather Division of Toxicological Sciences, John The Johns Hopkins University, …

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