| High prevalence of dysfibrinogenemia among patients with chronic thromboembolic pulmonary hypertension. | |
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MedLine Citation:
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PMID: 19420351 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The mechanism by which chronic thromboembolic pulmonary hypertension (CTEPH) develops after acute pulmonary thromboembolism is unknown. We previously reported that fibrin from CTEPH patients is relatively resistant to fibrinolysis in vitro. In the present study, we performed proteomic, genomic, and functional studies on fibrin(ogen) to investigate whether abnormal fibrin(ogen) might contribute to the pathogenesis of CTEPH. Reduced and denatured fibrinogen from 33 CTEPH patients was subjected to liquid chromatography-mass spectrometry analysis. Fibrinogen from 21 healthy controls was used to distinguish atypical from commonly occurring mass peaks. Atypical peaks were further investigated by targeted genomic DNA sequencing. Five fibrinogen variants with corresponding heterozygous gene mutations (dysfibrinogenemias) were observed in 5 of 33 CTEPH patients: Bbeta P235L/gamma R375W, Bbeta P235L/gamma Y114H, Bbeta P235L, Aalpha L69H, and Aalpha R554H (fibrinogens(San Diego I-V)). Bbeta P235L was found in 3 unrelated CTEPH patients. Functional analysis disclosed abnormalities in fibrin polymer structure and/or lysis with all CTEPH-associated mutations. These results suggest that, in some patients, differences in the molecular structure of fibrin may be implicated in the development of CTEPH after acute thromboembolism. |
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Authors:
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Timothy A Morris; James J Marsh; Peter G Chiles; Marisa M Magaña; Ni-Cheng Liang; Xavier Soler; Daniel J Desantis; Debby Ngo; Virgil L Woods |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-05-06 |
Journal Detail:
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Title: Blood Volume: 114 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-08-28 Completed Date: 2009-09-22 Revised Date: 2010-09-27 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 1929-36 Citation Subset: AIM; IM |
Affiliation:
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Division of Pulmonary and Critical Care Medicine, University of California, San Diego, CA 92103-8378, USA. t1morris@ucsd.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Blood Coagulation Disorders, Inherited / complications*, epidemiology* DNA Mutational Analysis Female Fibrin / metabolism Fibrinogen / genetics* Fibrinogens, Abnormal / genetics* Humans Hypertension, Pulmonary / complications*, epidemiology*, genetics Male Middle Aged Mutation Polymorphism, Genetic Prevalence Pulmonary Embolism / complications*, epidemiology*, genetics |
| Grant Support | |
ID/Acronym/Agency:
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2 P30CA023100-23/CA/NCI NIH HHS; AI076961/AI/NIAID NIH HHS; CA099835/CA/NCI NIH HHS; CA118595/CA/NCI NIH HHS; HL-080302/HL/NHLBI NIH HHS; HL-095089/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fibrinogens, Abnormal; 9001-31-4/Fibrin; 9001-32-5/Fibrinogen |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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