Role of Sphingolipid pathways in the pathobiology of PAH

鞘脂通路在 PAH 病理学中的作用

• 批准号: 10645008
• 负责人: Roberto F. Machado
• 金额: $ 68.8万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-05 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10645008
• 关键词: Address; Affinity; Apoptotic; Area; Bioenergetics; Blood Vessels; Blood flow; Cell Proliferation; Cells; Ceramides; Cessation of life; Clinical; Data; Deterioration; Development; Disease; E2F transcription factors; Endothelial Cells; Epigenetic Process; Event; Family; Functional disorder; Funding; G-Protein-Coupled Receptors; GPR12 gene; GPR3 gene; GPR6 gene; Gene Expression; Generations; Genes; Hypoxia; In Vitro; Lung; Lung diseases; Mammalian Cell; Mitochondria; Molecular; Pathogenesis; Pathway interactions; Patients; Phenotype; Physiological; Process; Proteins; Pulmonary Hypertension; Pulmonary arterial remodeling; Pulmonary artery structure; Role; SPHK1 enzyme; Signal Transduction; Smooth Muscle Myocytes; Sphingolipids; Sphingosine; Translations; Untranslated RNA; Vascular remodeling; Vasodilation; Ventricular; Vision; Workload; cellular targeting; chromatin remodeling; constriction; in vivo; lipid phosphate phosphatase; lung pressure; mortality; novel; novel therapeutics; phosphoethanolamine; premature; pulmonary arterial hypertension; pulmonary arterial pressure; pulmonary vascular remodeling; response; right ventricular failure; sphingosine 1-phosphate; sphingosine kinase; sphingosine-1-phosphate lyase; sphingosine-1-phosphate phosphatase; therapeutic target; vascular smooth muscle cell proliferation

ABSTRACT Pulmonary arterial hypertension (PAH), a rare, debilitating and fatal disease for which there is currently no available cure. There is compelling evidence that the Sphingosine kinase1/S1P signaling axis is a novel and therapeutic target for PAH. To facilitate the translation of current in vivo and in vitro observations on the role of S1P dependent signaling in PAH pathobiology, this proposal will explore the hypothesis that the Sphingosine kinase1/S1P signaling axis regulates physiologic, cellular and molecular pathways in PAH that result in pulmonary vascular remodeling. SA1 seeks to define the role of LncRNA Khps1 in miR-1 and SPHK1 expression and promoting pulmonary vascular remodeling. SA2 seeks to define molecular mechanisms by which LncRNA Khps1/SPHK1 regulate pulmonary artery smooth muscle cell mitochondrial dynamics. SA3 will investigate the role of SPHK1 in aberrant chromatin remodeling and gene expression in the development of pulmonary vascular remodeling.

摘要

项目成果

Progressive glomerular and tubular damage in sickle cell trait and sickle cell anemia mouse models.

• DOI: 10.1016/j.trsl.2018.01.007
• 发表时间: 2018-07
• 期刊: Translational research : the journal of laboratory and clinical medicine
• 作者: Saraf SL;Sysol JR;Susma A;Setty S;Zhang X;Gudehithlu KP;Arruda JAL;Singh AK;Machado RF;Gordeuk VR
• 通讯作者: Gordeuk VR

Pulmonary hypertension associated with thalassemia syndromes.

• DOI: 10.1111/nyas.13037
• 发表时间: 2016-03
• 期刊: Annals of the New York Academy of Sciences
• 影响因子: 5.2
• 作者: Fraidenburg DR;Machado RF
• 通讯作者: Machado RF

Endothelial nitric oxide synthase genotype is associated with pulmonary hypertension severity in left heart failure patients.

• DOI: 10.1177/2045894018773049
• 发表时间: 2018-04
• 期刊: Pulmonary circulation
• 影响因子: 2.6
• 作者: Duarte JD;Kansal M;Desai AA;Riden K;Arwood MJ;Yacob AA;Stamos TD;Cavallari LH;Zamanian RT;Shah SJ;Machado RF
• 通讯作者: Machado RF

Nuclear Sphingosine-1-phosphate Lyase Generated ∆2-hexadecenal is A Regulator of HDAC Activity and Chromatin Remodeling in Lung Epithelial Cells.

• DOI: 10.1007/s12013-021-01005-9
• 发表时间: 2021-09
• 期刊: Cell biochemistry and biophysics
• 影响因子: 2.6
• 作者: Ebenezer DL;Ramchandran R;Fu P;Mangio LA;Suryadevara V;Ha AW;Berdyshev E;Van Veldhoven PP;Kron SJ;Schumacher F;Kleuser B;Natarajan V
• 通讯作者: Natarajan V

Interaction Between Pannexin 1 and Caveolin-1 in Smooth Muscle Can Regulate Blood Pressure.

• DOI: 10.1161/atvbaha.118.311290
• 发表时间: 2018-09
• 期刊: Arteriosclerosis, thrombosis, and vascular biology
• 作者: DeLalio LJ;Keller AS;Chen J;Boyce AKJ;Artamonov MV;Askew-Page HR;Keller TCS 4th;Johnstone SR;Weaver RB;Good ME;Murphy SA;Best AK;Mintz EL;Penuela S;Greenwood IA;Machado RF;Somlyo AV;Swayne LA;Minshall RD;Isakson BE
• 通讯作者: Isakson BE