Document Detail


Paradoxical absence of a prothrombotic phenotype in a mouse model of severe hyperhomocysteinemia.
MedLine Citation:
PMID:  22186991     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hyperhomocysteinemia confers a high risk for thrombotic vascular events, but homocysteine-lowering therapies have been ineffective in reducing the incidence of secondary vascular outcomes, raising questions regarding the role of homocysteine as a mediator of cardiovascular disease. Therefore, to determine the contribution of elevated homocysteine to thrombosis susceptibility, we studied Cbs(-/-) mice conditionally expressing a zinc-inducible mutated human CBS (I278T) transgene. Tg-I278T Cbs(-/-) mice exhibited severe hyperhomocysteinemia and endothelial dysfunction in cerebral arterioles. Surprisingly, however, these mice did not display increased susceptibility to arterial or venous thrombosis as measured by photochemical injury in the carotid artery, chemical injury in the carotid artery or mesenteric arterioles, or ligation of the inferior vena cava. A survey of hemostatic and hemodynamic parameters revealed no detectible differences between control and Tg-I278T Cbs(-/-) mice. Our data demonstrate that severe elevation in homocysteine leads to the development of vascular endothelial dysfunction but is not sufficient to promote thrombosis. These findings may provide insights into the failure of homocysteine-lowering trials in secondary prevention from thrombotic vascular events.
Authors:
Sanjana Dayal; Anil K Chauhan; Melissa Jensen; Lorie Leo; Cynthia M Lynch; Frank M Faraci; Warren D Kruger; Steven R Lentz
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-12-20
Journal Detail:
Title:  Blood     Volume:  119     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-30     Completed Date:  2012-05-25     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3176-83     Citation Subset:  AIM; IM    
Affiliation:
Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA. sanjana-dayal@uiowa.edu
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Cystathionine beta-Synthase / genetics
Disease Models, Animal*
Female
Hematologic Tests
Hemodynamics / genetics,  physiology
Humans
Hyperhomocysteinemia / blood,  complications*,  genetics,  pathology*
Male
Mice*
Mice, Inbred C57BL
Mice, Knockout
Phenotype
Risk Factors
Severity of Illness Index
Thrombosis / etiology*
Grant Support
ID/Acronym/Agency:
HL062984/HL/NHLBI NIH HHS; HL063943/HL/NHLBI NIH HHS; NS024621/NS/NINDS NIH HHS; P01 NS024621/NS/NINDS NIH HHS; R01 HL063943/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
EC 4.2.1.22/Cystathionine beta-Synthase
Comments/Corrections
Comment In:
Blood. 2012 Mar 29;119(13):2977-8   [PMID:  22461473 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Serotonin 5-HT2B receptors are required for bone-marrow contribution to pulmonary arterial hypertens...
Next Document:  Therapeutic applications of macrophage colony-stimulating factor-1 (CSF-1) and antagonists of CSF-1 ...