Blood, 1 March 2003, Vol. 101, No. 5, pp. 1871-1873
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Brief report
Myocardial fibrosis in mice with overexpression of human
blood coagulation factor IX
Afshin Ameri,
Sumiko Kurachi,
Katsuo Sueishi,
Mitsuhiro Kuwahara, and
Kotoku Kurachi
From the Department of Human Genetics, University of
Michigan Medical School, Ann Arbor, MI; and the Department of
Pathology, Faculty of Medicine, Kyushu University, Fukuoka,
Japan.
Elevated circulatory levels of many blood coagulation factors are
known to be a risk factor for deep vein thrombosis in humans. Here we
report the first direct demonstration of a close association between
elevated circulatory factor IX levels in mice with thrombosis as well
as myocardial fibrosis. Transgenic mice overexpressing human factor IX
at persistently high levels died at much younger ages than their
cohorts expressing lower levels, or nontransgenic control animals. The
median survival age of animals was inversely related to the circulatory
levels of human factor IX. Prematurely dying animals had focal
fibrotic lesions predominantly present in the left ventricular
myocardium, and vasculatures in these lesions showed fibrin deposition.
Thromboemboli were also present in other organs, including lung and
brain. These observations support the hypothesis that
persistently high circulatory levels of factor IX are a risk factor not
only for thrombosis and/or thromboembolism, but also for myocardial
fibrosis mimicking human myocardial infarction.
