CORE B: This Core supports the Projects in this application through three functions. These are: Function 1) to coordinate recruitment of PAH patients and controls, clinically evaluate enrollees and conduct sample collection;Function 2) establish and maintain a biospecimen repository and distribute its resources (serum, plasma, circulating cells, cultured fibroblasts, DNA, RNA, banked tissue samples) to Projects 1, 2 and 3 and to collaborators at Columbia and for other NIH funded investigators;Function 3) facilitate analysis of data, especially human data in Projects 1, 2 and 3. The idiopathic PAH patients will largely be drawn from our Center for Pulmonary Vascular Disease, a clinical center that has nearly 450 reference patients and has successfully participated in over 20 national clinical trials over the last decade. Controls will come from the Vanderbilt General Clinical Research Center bank (ResearchMatch.com) and from within families. We use a national specimen and survey company for offsite collection of specimens. HPAH patients will also be recruited from Columbia University through an ongoing collaboration with Dr. Wendy Chung who runs the PH genetics component of the Columbia PH group. In Function 2, blood, urine, fibroblasts, cells, DNA, RNA and tissue will be generated, processed and stored in the laboratories of the Pulmonary Circulation Genomics Center, the Vanderbilt DNA Resource Core and the laboratories of the Pulmonary Division. Management of the entire collection will be done by dedicated personnel using the comprehensive REDCap data base. We have a history of over 2 thousand total subjects in our database, including the Progeny Software used for genetic and family data, and can move DNA, RNA, data and materials reliably and accurately. Function 3 is the analysis of data created largely in Projects 1 and 2. The development and design of experiments has been aided by our Epidemiologist and Statistician who will be the statistical coordinator for the entire PPG, including powering, sample size, estimates, outcome measures, data check and quality control, application of appropriate biostatlstical tests depending on data sets and hypotheses. Thus statistical support is fully integrated into the design, conduct and analysis.
Pulmonary arterial hypertension (PAH) is elevated blood pressure in the lungs, which leads to right heart failure and death. No existing treatments are very effective. This Program Project Grant aims to develop new, more effective treatments based on interventions against the hormonal, metabolic, and signaling defects recently shown to form the molecular basis for disease. Core B supports these functions.
|Chen, Xinping; Talati, Megha; Fessel, Joshua P et al. (2016) Estrogen Metabolite 16Î±-Hydroxyestrone Exacerbates Bone Morphogenetic Protein Receptor Type II-Associated Pulmonary Arterial Hypertension Through MicroRNA-29-Mediated Modulation of Cellular Metabolism. Circulation 133:82-97|
|Evans, Jonathan D W; Girerd, Barbara; Montani, David et al. (2016) BMPR2 mutations and survival in pulmonary arterial hypertension: an individual participant data meta-analysis. Lancet Respir Med 4:129-37|
|Hemnes, Anna R; Zhao, Min; West, James et al. (2016) Critical Genomic Networks and Vasoreactive Variants in Idiopathic Pulmonary Arterial Hypertension. Am J Respir Crit Care Med 194:464-75|
|Talati, Megha H; Brittain, Evan L; Fessel, Joshua P et al. (2016) Mechanisms of Lipid Accumulation in the Bone Morphogenetic Protein Receptor Type 2 Mutant Right Ventricle. Am J Respir Crit Care Med 194:719-28|
|Hay, Bryan R; Pugh, Meredith E; Robbins, Ivan M et al. (2016) Parenteral Prostanoid Use at a Tertiary Referral Center: A Retrospective Cohort Study. Chest 149:660-6|
|West, James D; Carrier, Erica J; Bloodworth, Nathaniel C et al. (2016) Serotonin 2B Receptor Antagonism Prevents Heritable Pulmonary Arterial Hypertension. PLoS One 11:e0148657|
|Brittain, Evan L; Talati, Megha; Fessel, Joshua P et al. (2016) Fatty Acid Metabolic Defects and Right Ventricular Lipotoxicity in Human Pulmonary Arterial Hypertension. Circulation 133:1936-44|
|Chung, Wendy K; Austin, Eric D; Best, D Hunter et al. (2015) When to offer genetic testing for pulmonary arterial hypertension. Can J Cardiol 31:544-7|
|Hemnes, Anna R; Trammell, Aaron W; Archer, Stephen L et al. (2015) Peripheral blood signature of vasodilator-responsive pulmonary arterial hypertension. Circulation 131:401-9; discussion 409|
|Newman, John H; Brittain, Evan L; Robbins, Ivan M et al. (2015) Effect of acute arteriolar vasodilation on capacitance and resistance in pulmonary arterial hypertension. Chest 147:1080-5|
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