T. Matsumoto et al., INFLUENCE OF FK506 ON EXPERIMENTAL ATHEROSCLEROSIS IN CHOLESTEROL-FEDRABBITS, Atherosclerosis (Amsterdam), 139(1), 1998, pp. 95-106
To investigate the role of activated T lymphocytes in the formation of
atherosclerotic lesions, we studied the influence of FK506, an immuno
suppressant, on the development of atherosclerosis in cholesterol-fed
rabbits. New Zealand White rabbits fed on a 1.5% cholesterol diet were
administered FK506 at 0.05 mg/kg (n = 12), 0.1 mg/kg (n = 12) or isot
onic saline (as the control, n = 12) intramuscularly three times a wee
k for 12 weeks. Although FK506 treatment did not affect plasma lipid l
evels, it caused an increase in the development of atherosclerotic les
ions in a dose-dependent manner. Immunohistochemical analysis of the a
orta after 8 weeks on the diet revealed that the ratio of T lymphocyte
s to the total number of cells in the plaques decreased significantly
in the FK506 treated rabbits compared to the control rabbits. In cultu
re, FK506 did not affect smooth muscle cell proliferation and choleste
ryl ester formation in the macrophages. In contrast, culture medium fr
om lymphocytes stimulated by concanavalin A decreased the accumulation
of cholesteryl ester in the macrophages. This effect was inhibited by
the culture medium in the presence of FK506. These findings suggest t
hat activated T lymphocytes may inhibit intracellular cholesterol accu
mulation in atherosclerotic plaque. (C) 1998 Elsevier Science Ireland
Ltd. All rights reserved.