Mast cells are important cells of the immune system and are recognized as participants in the pathogenesis of
atherosclerosis. In this study, we evaluated the role of mast cells on the progression of
atherosclerosis and hepatic steatosis using the
apolipoprotein E-deficient (
ApoE(-/-)) and
ApoE(-/-)/mast cell-deficient (Kit(W-sh/W-sh)) mouse models maintained on a high-fat diet. The en face analyses of aortas showed a marked reduction in plaque coverage in
ApoE(-/-)/Kit(W-sh/W-sh) compared with
ApoE(-/-) after a 6-mo regimen with no significant change noted after 3 mo. Quantification of intima/media thickness on
hematoxylin and
eosin-stained histological cross sections of the aortic arch revealed no significant difference between
ApoE(-/-) and
ApoE(-/-)/Kit(W-sh/W-sh) mice. The high-fat regimen did not induce
atherosclerosis in either Kit(W-sh/W-sh) or wild-type mice. Mast cells with indications of degranulation were seen only in the aortic walls and heart of
ApoE(-/-) mice. Compared with
ApoE(-/-) mice, the serum levels of total
cholesterol,
low-density lipoprotein and
high-density lipoprotein were decreased by 50% in
ApoE(-/-)/Kit(W-sh/W-sh) mice, whereas no appreciable differences were noted in serum levels of
triglycerides or
very low density lipoprotein.
ApoE(-/-)/Kit(W-sh/W-sh) mice developed significantly less hepatic steatosis than
ApoE(-/-) mice after the 3-mo regimen. The analysis of Th1/Th2/Th17
cytokine profile in the sera revealed significant reduction of
interleukin (IL)-6 and
IL-10 in
ApoE(-/-)/Kit(W-sh/W-sh) mice compared with
ApoE(-/-) mice. The assessment of systemic generation of
thromboxane A(2) (TXA(2)) and
prostaglandin I(2) (PGI(2)) revealed significant decrease in the production of PGI(2) in
ApoE(-/-)/Kit(W-sh/W-sh) mice with no change in TXA(2). The decrease in PGI(2) production was found to be associated with reduced levels of
cyclooxygenase-2 mRNA in the aortic tissues. A significant reduction in T-lymphocytes and macrophages was noted in the
atheromas of the
ApoE(-/-)/Kit(W-sh/W-sh) mice. These results demonstrate the direct involvement of mast cells in the progression of
atherosclerosis and hepatic steatosis.