Integrative Physiology |
From the First Department of Internal Medicine, Niigata University School of Medicine (M.I., M.K., M.M., M.Y., K.F., Y.U., S.H., Y.O., K.K., Y.A.), and Research Laboratory for Molecular Genetics, Niigata University (Y.H., T.H., R.K.), Niigata, Japan.
Correspondence to Masahiro Ito, MD, First Department of Internal Medicine, Niigata University School of Medicine, 1-757 Asahimachi, Niigata 951-8510, Japan.
AbstractThe expression of coxsackievirus and adenovirus receptor (CAR) was dominant in the brains and hearts of mice until the newborn phase. There is no detailed information concerning the relation between the expression of CAR and development of hearts. It is also uncertain whether CAR is able to be induced in adult hearts after cardiac injury. We demonstrated that CAR was abundant in the hearts of newborn rats but was barely detectable in the hearts of adult rats. The expression of CAR in rat hearts with experimental autoimmune myocarditis, which was induced by immunization of purified cardiac myosin, was serially investigated. Active myocarditis was observed from day 15 after immunization. By immunohistochemistry, cardiomyocytes were strongly stained for CAR antibody from days 24 to 42. CAR mRNA was also detected from days 18 to 30 by using reverse transcriptionpolymerase chain reaction. In the next experiment, the induction of CAR on isolated cardiomyocytes was investigated. CAR was barely detectable in cultured cardiomyocytes by Western blot analysis after isolation. This molecule gradually appeared along with the creation of clusters and beating of cardiomyocytes. Furthermore, the induction of CAR in cultured cardiomyocytes increased after supplement with conditioned medium of rat splenocytes activated by concanavalin A. In conclusion, rat CAR is expressed strongly in the hearts of newborn rats and is suppressed in those of adult rats. The expression of CAR is enhanced during the active phase of experimental autoimmune myocarditis and is induced by inflammatory mediators. CAR may play a role in cell-to-cell contact and adhesion of cardiomyocytes.
Key Words: coxsackievirus and adenovirus receptors myocarditis cardiomyocytes
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