NAD-dependent Signaling and Pulmonary Vascular Remodeling in PAH

PAH 中 NAD 依赖性信号传导和肺血管重塑

• 批准号: 10581570
• 负责人: Roberto F. Machado
• 金额: $ 71.04万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10581570
• 关键词: Address; Anabolism; Animal Model; Apoptosis; Biochemical; Biological Markers; Blood Vessels; Cell Proliferation; Cell Survival; Cells; Characteristics; Data; Development; Disease; Endothelial Cells; Experimental Animal Model; Functional disorder; Gene Expression Profile; Generations; Genetic; Genetic Transcription; Genetic Variation; Growth Factor; In Situ; In Vitro; Inflammatory; Inflammatory Response; Injury; Link; Malignant Neoplasms; Mediator; Metabolic; Mitochondria; Molecular; Niacinamide; Oxidation-Reduction; Pathogenesis; Pathologic; Pathway interactions; Patients; Phenotype; Physiological; Plasma; Play; Predisposition; Process; Production; Prognosis; Proliferating; Proteins; Publishing; Pulmonary Hypertension; Pulmonary artery structure; Regulation; Resistance; Role; Signal Transduction; Smooth Muscle Myocytes; Testing; Thrombosis; Translations; Vascular remodeling; Vision; biological adaptation to stress; cell growth regulation; cell motility; chemotherapeutic agent; cytokine; extracellular; in vivo; mortality; nicotinamide phosphoribosyltransferase; novel; novel marker; pharmacologic; precursor cell; predicting response; pulmonary arterial hypertension; pulmonary artery endothelial cell; pulmonary vascular remodeling; response; senescence; therapeutic target; translational study; vascular inflammation; vasoconstriction

ABSTRACT Pulmonary arterial hypertension (PAH), a rare, debilitating and fatal disease for which there is currently no available cure. There is compelling evidence that NAD-dependent signaling via NAMPT is a novel and therapeutic target for PAH. To facilitate the translation of current in vivo and in vitro observations on the role of NAMPT dependent signaling in PAH pathobiology, this proposal will explore the hypothesis that the NAMPT/NAD signaling axis regulates physiologic, cellular and molecular pathways in PAH that result in pulmonary vascular remodeling. SA1 seeks to define the role of pulmonary artery endothelial cell NAMPT in the regulation on metabolic reprograming associated with the PH response. SA2 define the role of NAMPT in regulating mitochondrial dynamics in pulmonary artery endothelial cells. SA3 will seek discover and validate biochemical and genetic NAMPT-centric biomarkers of PAH susceptibility and prognosis.

抽象的 肺动脉高压（PAH），一种罕见的，令人衰弱的致命疾病，目前没有 可用治疗。有令人信服的证据表明，通过NAMPT通过NAD依赖性信号传导是一种新颖， PAH的治疗靶标。促进当前体内和体外观察的翻译 NAMPT依赖信号在PAH病理生物学中的作用，该提案将探讨以下假设。 NAMPT/NAD信号轴调节PAH中的生理，细胞和分子途径 肺血管重塑。 SA1试图定义肺动脉内皮细胞NAMPT的作用 与pH反应相关的代谢重编程的调节。 SA2定义了NAMPT在 调节肺动脉内皮细胞中的线粒体动力学。 SA3将寻求发现并验证 PAH敏感性和预后的生化和遗传NAMPTIC的生物标志物。