Emerging evidence intimates that lung macro- and microvascular endothelial cells arise from distinct embryological (e.g. epigenetic) origins and, further, that these cells remain differentiated throughout embryonic, fetal and adult life. Thus, macro- and microvascular endothelial cell phenotype is controlled by both epigenetic and environmental factors. Interplay between epigenetic and environmental control of cell phenotype is poorly understood, and the clinical implications of such phenotype regulation have only recently been considered. Thus, this application seeks funding to support the 2004 Grover Conference on the Pulmonary Circulation, entitled Genetic and Environmental Determinants of Pulmonary Endothelial Cell Function, to assess the interplay between epigenetic and environmental regulation of endothelial cell phenotype. Specifically, the 2004 Grover Conference seeks to provide a forum for experts in endothelial cell and vascular biology to rigorously address: (1) The epigenetic origin of macro- and microvascular endothelial cells; (2) Control of cell function through activation of unique signaling networks in phenotypically distinct endothelia; (3) Endothelial cell plasticity; and, (4) Endothelium as a therapeutic target in medicine. Proceedings from this meeting will be disseminated as a special book edition, published by Futura. We request funding for partial support of travel and lodging for speakers. The 2004 Grover Conference will be the 12th in this series, representing the longest-standing conference on the Pulmonary Circulation, and will be held at the Lost Valley Ranch in Sedalia, Colorado. As in earlier formats, equal time will be given to presentation and discussion to optimize scientific interchange among experts in the field. At the conclusion of this meeting and as part of the published report, we will have identified areas of need for future investigation in lung vascular biology. [unreadable] [unreadable]