Pulmonary Hypertension Breakthrough Initiative

肺动脉高压突破计划

• 批准号: 9307972
• 负责人: Micheala A Aldred
• 金额: $ 250.73万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-10-30 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9307972
• 关键词: Alabama; American; Bioinformatics; Blood; Blood Pressure; Blood Vessels; Blood specimen; Cardiac; Cardiovascular system; Cataloging; Catalogs; Categories; Cell Line; Cell Separation; Cells; Clinic; Clinical; Colorado; Competence; Consult; Consultations; DNA analysis; Data; Data Analyses; Data Coordinating Center; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Enrollment; Funding; Future; Genetic; Genomics; Goals; Heart; Human; Incidence; Informatics; Inherited; Institutes; Investigation; Lung; Lung Transplantation; Lung diseases; Medical Research; Michigan; Monoclonal Antibody R24; Morphology; Mutation; National Heart, Lung, and Blood Institute; Pathologic; Pathology; Patients; Pennsylvania; Pharmaceutical Preparations; Phenotype; Physiological; Predisposition; Process; Pulmonary Hypertension; Pulmonary artery structure; RNA analysis; Recording of previous events; Research; Research Design; Research Infrastructure; Research Personnel; Research Support; Resources; Risk Factors; Role; Site; Specimen; Time; Tissues; Translations; Transplant Recipients; Universities; Woman; Work; base; biobank; blood pump; clinical care; education research; effective therapy; flexibility; heart cell; high throughput analysis; human tissue; hypertension control; hypertensive heart disease; meetings; member; mortality; novel; novel diagnostics; public health relevance; pulmonary arterial hypertension; success

DESCRIPTION (provided by applicant): Pulmonary Arterial Hypertension (PAH) is a heterogeneous group of diseases with high mortality, difficult diagnosis, limited available treatment, and no cure. The Pulmonary Hypertension Breakthrough Initiative (PHBI) is dedicated to comprehensive biobanking of human lungs with PAH and controls, supported by a detailed clinical annotation of the accrued specimens. Having started in 2006, the PHBI successfully developed a novel and unique infrastructure, whose success relied on the active participation of a highly integrated network of university-based sites with extensive expertise in each of the spheres of competency: excellence in clinical care of PAH (including patient accruals), lung transplantation, pathology, genetics, genomics, and cell isolation. The goal of this application is to leverage these unparalled resources and unique expertise into an R24-supported initiative to direct the bank to accrue specimens of disease-specific groups, which will be highly integrated with pathologic, genetic, and genomic subphenotypes pertaining to not only lung and blood specimens, but now expanding to the failing PAH heart. This proposal will be highly synergistic with the presently supported initiatives by the NHLBI in the field. The flexibilty of our infrastructure and governance will allow us to be decidedly responsive and integrated with any future NHLBI initiatives. We propose that this unique infrastructure will serve the pressing roles of advancing the translation of key discoveries to the patients with PAH and to aid in new discoveries that will have a long lasting impact in the field. The following specific aims will be pursued: Specific Aims of the Proposal 1) To establish a comprehensive biorepository of the specimens from subjects with pulmonary arterial hypertension and failed donor controls. 2) To provide the infrastructure to support human tissue based research in PAH via integrated cores devoted to Administration, Tissue Handling and Pathology, Cell Line Development, and Genomic Characterization and Cataloging. 3) To develop and implement an interface for consultation of research design and analysis to enhance broader scientific investigation.

描述（由申请人提供）：肺动脉高压（PAH）是一种异质性疾病，死亡率高，诊断困难，治疗有限，无法治愈。肺动脉高压突破倡议（PHBI）致力于对具有多环芳烃和对照的人肺进行全面的生物银行，并对累积标本进行详细的临床注释。自2006年成立以来，PHBI成功地开发了一个新颖而独特的基础设施，其成功依赖于一个高度整合的大学网站网络的积极参与，这些网站在每个能力领域都具有广泛的专业知识：PAH的卓越临床护理（包括患者累积），肺移植，病理学，遗传学，基因组学和细胞分离。该应用程序的目标是将这些无与伦比的资源和独特的专业知识运用到r24支持的倡议中，以指导银行积累疾病特定组的标本，这些标本将与病理、遗传和基因组亚表型高度整合，不仅与肺和血液标本有关，而且现在扩展到衰竭的PAH心脏。这一建议将与国家卫生和贷款机构目前在外地支持的倡议高度协同。我们的基础设施和治理的灵活性将使我们能够果断地响应并整合任何未来的NHLBI计划。我们建议，这种独特的基础设施将发挥推动关键发现转化为PAH患者的紧迫作用，并有助于在该领域产生长期影响的新发现。将实现下列具体目标：

项目成果

Inhibition of Anaplerosis Attenuated Vascular Proliferation in Pulmonary Arterial Hypertension.

抑制肺动脉高压中的回补减弱血管增殖。

• DOI: 10.3390/jcm9020443
• 发表时间: 2020
• 期刊: Journal of clinical medicine
• 影响因子: 3.9
• 作者: ValuparampilVarghese,Mathews;James,Joel;Eccles,CodyA;Niihori,Maki;Rafikova,Olga;Rafikov,Ruslan
• 通讯作者: Rafikov,Ruslan

Antioxidant-Conjugated Peptide Attenuated Metabolic Reprogramming in Pulmonary Hypertension.

抗氧化剂缀合肽减弱肺动脉高压的代谢重编程。

• DOI: 10.3390/antiox9020104
• 发表时间: 2020
• 期刊: Antioxidants (Basel, Switzerland)
• 作者: Varghese,MathewsValuparampil;Niihori,Maki;Eccles,CodyA;Kurdyukov,Sergey;James,Joel;Rafikova,Olga;Rafikov,Ruslan
• 通讯作者: Rafikov,Ruslan

Pulmonary Arterial Hypertension Induces a Distinct Signature of Circulating Metabolites.

肺动脉高压会引起循环代谢物的独特特征。

• DOI: 10.3390/jcm9010217
• 发表时间: 2020
• 期刊: Journal of clinical medicine
• 影响因子: 3.9
• 作者: Rafikov,Ruslan;Coletta,DawnK;Mandarino,LawrenceJ;Rafikova,Olga
• 通讯作者: Rafikova,Olga