| First Author | Pawlinski R | Year | 2002 |
| Journal | Proc Natl Acad Sci U S A | Volume | 99 |
| Issue | 24 | Pages | 15333-8 |
| PubMed ID | 12426405 | Mgi Jnum | J:80537 |
| Mgi Id | MGI:2446024 | Doi | 10.1073/pnas.242501899 |
| Citation | Pawlinski R, et al. (2002) Tissue factor deficiency causes cardiac fibrosis and left ventricular dysfunction. Proc Natl Acad Sci U S A 99(24):15333-8 |
| abstractText | Exposure of blood to tissue factor (TF) activates the extrinsic (TF:FVIIa) and intrinsic (FVIIIa:FIXa) pathways of coagulation. In this study, we found that mice expressing low levels of human TF ( approximately 1% of wild-type levels) in an mTF(-/-) background had significantly shorter lifespans than wild-type mice, in part, because of spontaneous fatal hemorrhages. All low-TF mice exhibited a selective heart defect that consisted of hemosiderin deposition and fibrosis. Direct intracardiac measurement demonstrated a 30% reduction (P < 0.001) in left ventricular function in 8-month-old low-TF mice compared with age-matched wild-type mice. Mice expressing low levels of murine FVII ( approximately 1% of wild-type levels) exhibited a similar pattern of hemosiderin deposition and fibrosis in their hearts. In contrast, FIX(-/-) mice, a model of hemophilia B, had normal hearts. Cardiac fibrosis in low-TF and low-FVII mice appears to be caused by hemorrhage from cardiac vessels due to impaired hemostasis. We propose that TF expression by cardiac myocytes provides a secondary hemostatic barrier to protect the heart from hemorrhage. |
