| Lung 18F-fluorodeoxyglucose PET for Diagnosis and Monitoring of Pulmonary Arterial Hypertension. | |
| | |
MedLine Citation:
|
PMID: 22246173 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
RATIONALE: Pulmonary arterial hypertension (PAH) is a proliferative arteriopathy associated with glucose transporter 1 (Glut1) upregulation and a glycolytic shift in lung metabolism. Glycolytic metabolism can be detected using the Positron Emission Tomography(PET) tracer, 18F-fluorodeoxyglucose (FDG). OBJECTIVES: The precise cell type in which glycolytic abnormalities occur in PAH is unknown. Moreover, whether FDG-PET is sufficiently sensitive to monitor PAH progression and detect therapeutic regression is untested. We hypothesized that increased lung FDG-PET reflects enhanced glycolysis in vascular cells and is reversible in response to effective therapies. METHODS: PAH was induced in Sprague-Dawley rats by monocrotaline or chronic hypoxia (FiO2 10%) in combination with Sugen 5416. Monocrotaline rats were treated with oral dichloroacetate or daily Imatinib injections. FDG-PET scans and pulmonary artery acceleration times were obtained weekly. The PET signal's origin was assessed using laser capture microdissection of airway versus vascular tissue. Metabolism was measured in pulmonary artery smooth muscle cell (PASMC) cultures using a Seahorse analyzer. MEASUREMENTS AND MAIN RESULTS: Lung FDG increases 1-2 weeks after monocrotaline (when PAH is mild) and is normalized by dichloroacetate and Imatinib, which both also regress medial hypertrophy. Glut1 mRNA is upregulated in both endothelium and PASMCs, but not airway cells or macrophages. PASMCs from monocrotaline rats are hyperproliferative and display normoxic activation of hypoxia-inducible factor-1α (HIF-1α), which underlies their glycolytic phenotype. CONCLUSIONS: HIF-1α-mediated Glut1 upregulation in proliferating vascular cells in PAH accounts for increased lung FDG-PET uptake. FDG-PET is sensitive to mild PAH and can monitor therapeutic changes in the vasculature. |
| | |
Authors:
|
Glenn Marsboom; Christian Wietholt; Chad R Haney; Peter T Toth; John J Ryan; Erik Morrow; Thenappan Thenappan; Peter Bache-Wiig; Lin Piao; Jonathan Paul; Chin-Tu Chen; Stephen L Archer |
Related Documents
:
|
2669643 - Freehand homograft aortic valve replacement--the learning curve: a technical analysis o... 15870043 - Left ventricular outflow tract false aneurysm late after aortic valve replacement. 11252693 - Vasculitis of the internal carotid artery in wegener's granulomatosis: comparison of ul... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-1-12 |
Journal Detail:
|
Title: American journal of respiratory and critical care medicine Volume: - ISSN: 1535-4970 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
|
Created Date: 2012-1-16 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9421642 Medline TA: Am J Respir Crit Care Med Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Cardiology, University of Chicago, Chicago, Illinois, United States. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Unsymmetrical diarylethenes as molecular keypad locks with tunable photochromism and fluorescence vi...
Next Document: Disruption of Platelet-derived Chemokine Heteromers Prevents Neutrophil Extravasation in Acute Lung ...