Role of cardiac myocyte tissue factor in heart hemostasis.
BACKGROUND
The tissue-specific pattern of tissue factor (TF) expression suggests that it plays a major role in the hemostatic protection of specific organs, such as the heart and lung. In support of this notion, we found that mice expressing very low levels of TF exhibit hemostatic defects in the heart and lung. Hemosiderosis and fibrosis are observed in the hearts of all low TF mice as early as 3 months of age. In contrast, TF(+/-) mice expressing approximately 50% of wild-type levels of TF had no detectable hemostatic defects.


OBJECTIVE
The objective of this study was to determine the threshold of TF that is required to maintain hemostasis under normal and pathologic conditions, and to investigate the specific role of cardiac myocyte TF in heart hemostasis using mice with altered levels of TF expression in cardiac myocytes.


RESULTS
First, we found that mice with 20% of wild-type levels of TF activity in their hearts had hemosiderosis and fibrosis by 6 months of age. Secondly, mice with a selective deletion of the TF gene in cardiac myocytes had a mild hemostatic defect under normal conditions but exhibited a significant increase in hemosiderosis and fibrosis after challenge with isoproterenol. Finally, we showed that cardiac myocyte-specific overexpression of TF abolished hemosiderin deposition and fibrosis in the hearts of low TF mice.


CONCLUSIONS
Taken together, our results indicate that TF expression by cardiac myocytes is important to maintain heart hemostasis under normal and pathologic conditions.
Department of Immunology, The Scripps Research Institute, La Jolla, CA, USA.
R
R
Pawlinski
M
M
Tencati
T
T
Holscher
B
B
Pedersen
T
T
Voet
R E
RE
Tilley
P
P
Marynen
N
N
Mackman
D000818:Animals; D005838:Genotype; D006321:Heart / Q000502:physiology*; D006487:Hemostasis; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D013925:Thromboplastin / Q000235:genetics / Q000502:physiology; D014018:Tissue Distribution
D013925:Thromboplastin; D007545:Isoproterenol