Document Detail


High prevalence of dysfibrinogenemia among patients with chronic thromboembolic pulmonary hypertension.
MedLine Citation:
PMID:  19420351     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-05-06
Journal Detail:
Title:  Blood     Volume:  114     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-08-28     Completed Date:  2009-09-22     Revised Date:  2010-09-27    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1929-36     Citation Subset:  AIM; IM    
Affiliation:
Division of Pulmonary and Critical Care Medicine, University of California, San Diego, CA 92103-8378, USA. t1morris@ucsd.edu
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MeSH Terms
Descriptor/Qualifier:
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:
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:
0/Fibrinogens, Abnormal; 9001-31-4/Fibrin; 9001-32-5/Fibrinogen
Comments/Corrections

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