Primary Pulmonary Hypertension (PPH) is a devastating disease which occurs in a familial and in a sporadic form. The investigators have found that PPH is categorically different from plexogenic secondary pulmonary hypertension (2nd PH), in that the proliferative endothelial cells in PPH are mostly monoclonal, whereas they are strictly polyclonal in 2nd PH. The investigators postulate that the proliferating monoclonally expanding endothelial cells in PPH have properties of endothelial stem cells. Further, the investigators speculate that a) The pathogenesis of PPH can be understood by investigating the concept of misguided vasculogenesis/angiogenesis; b) That an aryl hydrocarbon receptor (AHR) -aryl hydrocarbon receptor nuclear transporter (ARNT) and hypoxia-inducible factor 1b (HIF-1b) interaction may be involved in pulmonary artery endothelial cell growth control. The PI's approach will be to obtain, via microdissection from PPH patient lungs, """"""""hypertensive"""""""" endothelial and vascular smooth muscle cells to generate cell-specific cDNA libraries, to apply the technique of serial analysis of gene expression (SAGE) and two-dimensional protein electrophoresis in order to characterize the gene and protein expression pattern of monoclonal and polyclonal """"""""hypertensive"""""""" pulmonary artery cells. The functional importance of the AHR/ARNT transcription system for pulmonary hypertensive endothelial cell growth will be examined in chronic shear stress exposed cell culture system using activators and inhibitors of AHR and a transcription factor decoy of the ARNT E box core sequence.
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