详情页 - 四川省肿瘤医院知识库

当前位置：首页 > 详情页

Purine synthesis suppression reduces the development and progression of pulmonary hypertension in rodent models

文献详情

资源类型：

Pubmed体系：

作者：

机构： [1]Vascular Biology Center, Medical College of Georgia, Augusta University, Sanders Building, CB-3919A, 1460 Laney Walker Blvd, Augusta, GA 30912-2500, USA [2]Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA [3]Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, Pennsylvania, PA 16802, USA [4]Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, China [5]Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Sanders Building, CB-3919A, 1460 Laney Walker Blvd, Augusta, GA 30912-2500, USA [6]Department of Neuroscience & Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA [7]Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania, PA 16802, USA [8]Department of Endocrinology, the First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei 230001, China [9]Division of Signal Transduction, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA [10]Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA [11]Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA

出处：

DOI：

ISSN：

摘要：

Proliferation of vascular smooth muscle cells (VSMCs) is a hallmark of pulmonary hypertension (PH). Proliferative cells utilize purine bases from the de novo purine synthesis (DNPS) pathways for nucleotide synthesis; however, it is unclear whether DNPS plays a critical role in VSMC proliferation during development of PH. The last two steps of DNPS are catalysed by the enzyme 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase (ATIC). This study investigated whether ATIC-driven DNPS affects the proliferation of pulmonary artery smooth muscle cells (PASMCs) and the development of PH.Metabolites of DNPS in proliferative PASMCs were measured by liquid chromatography-tandem mass spectrometry. ATIC expression was assessed in platelet-derived growth factor-treated PASMCs and in the lungs of PH rodents and patients with pulmonary arterial hypertension. Mice with global and VSMC-specific knockout of Atic were utilized to investigate the role of ATIC in both hypoxia- and lung interleukin-6/hypoxia-induced murine PH. ATIC-mediated DNPS at the mRNA, protein, and enzymatic activity levels were increased in platelet-derived growth factor-treated PASMCs or PASMCs from PH rodents and patients with pulmonary arterial hypertension. In cultured PASMCs, ATIC knockdown decreased DNPS and nucleic acid DNA/RNA synthesis, and reduced cell proliferation. Global or VSMC-specific knockout of Atic attenuated vascular remodelling and inhibited the development and progression of both hypoxia- and lung IL-6/hypoxia-induced PH in mice.Targeting ATIC-mediated DNPS compromises the availability of purine nucleotides for incorporation into DNA/RNA, reducing PASMC proliferation and pulmonary vascular remodelling and ameliorating the development and progression of PH.© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

基金：

语种：

PubmedID：

中科院(CAS)分区：

出版当年[2023]版：

大类 | 1 区

医学

小类 | 1 区心脏和心血管系统

最新[2023]版：

大类 | 1 区

医学

小类 | 1 区心脏和心血管系统

第一作者：

第一作者机构： [1]Vascular Biology Center, Medical College of Georgia, Augusta University, Sanders Building, CB-3919A, 1460 Laney Walker Blvd, Augusta, GA 30912-2500, USA

通讯作者：

通讯机构： [1]Vascular Biology Center, Medical College of Georgia, Augusta University, Sanders Building, CB-3919A, 1460 Laney Walker Blvd, Augusta, GA 30912-2500, USA [5]Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Sanders Building, CB-3919A, 1460 Laney Walker Blvd, Augusta, GA 30912-2500, USA

推荐引用方式(GB/T 7714)：

APA：

MLA：