Document Detail


A murine model of myocardial microvascular thrombosis.
MedLine Citation:
PMID:  10487767     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Disorders of hemostasis lead to vascular pathology. Endothelium-derived gene products play a critical role in the formation and degradation of fibrin. We sought to characterize the importance of these locally produced factors in the formation of fibrin in the cardiac macrovasculature and microvasculature. This study used mice with modifications of the thrombomodulin (TM) gene, the tissue-type plasminogen activator (tPA) gene, and the urokinase-type plasminogen activator (uPA) gene. The results revealed that tPA played the most important role in local regulation of fibrin deposition in the heart, with lesser contributions by TM and uPA (least significant). Moreover, a synergistic relationship in fibrin formation existed in mice with concomitant modifications of tPA and TM, resulting in myocardial necrosis and depressed cardiac function. The data were fit to a statistical model that may offer a foundation for examination of hemostasis-regulating gene interactions.
Authors:
P D Christie; J M Edelberg; M H Picard; A S Foulkes; W Mamuya; H Weiler-Guettler; R H Rubin; P Gilbert; R D Rosenberg
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  104     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1999 Sep 
Date Detail:
Created Date:  1999-10-04     Completed Date:  1999-10-04     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  533-9     Citation Subset:  AIM; IM    
Affiliation:
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cells, Cultured
Coronary Thrombosis / genetics,  metabolism*,  pathology
Disease Models, Animal*
Endothelium, Vascular / metabolism,  pathology
Fibrin / biosynthesis*
Fibrosis
Genetic Predisposition to Disease
Genotype
Hemostasis
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Microcirculation
Myocardium / pathology*
Thrombomodulin / deficiency,  genetics,  physiology*
Tissue Plasminogen Activator / deficiency,  genetics,  physiology*
Urokinase-Type Plasminogen Activator / deficiency,  genetics,  physiology*
Ventricular Dysfunction, Left / genetics,  ultrasonography
Grant Support
ID/Acronym/Agency:
HL-07604/HL/NHLBI NIH HHS; HL-41484/HL/NHLBI NIH HHS; P01-41484//PHS HHS
Chemical
Reg. No./Substance:
0/Thrombomodulin; 9001-31-4/Fibrin; EC 3.4.21.68/Tissue Plasminogen Activator; EC 3.4.21.73/Urokinase-Type Plasminogen Activator
Comments/Corrections

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