A Case-Reference Study on Plasma Fibrinogen Concentrations and Coronary Atherosclerosis in Japanese

Sato, Shinichi; Kobayashi, Takao; Iida, Minoru; Naito, Yoshihiko; Kiyama, Masahiko; Kitamura, Akihiko; Iso, Hiroyasu; Komachi, Yoshio

doi:10.2188/jea.6.81

Cited by 9 publications

(1 citation statement)

References 35 publications

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“…Fibrinogen concentrations have been significantly correlated with the likelihood of atherosclerotic cardiac events. 31,32 In rabbits, probucol showed an antiatherogenic effect in association with a reduction in fibrinogen concentrations (but no effect on cholesterol levels). 33 In the present study, FCP-3PI-treated animals had lower fibrinogen concentrations and fewer (and less severe) atherosclerotic lesions than either the control or probucol-treated groups.…”

Section: Discussionmentioning

confidence: 99%

Proatherogenic and Antiatherogenic Effects of Probucol and Phytosterols in Apolipoprotein E–Deficient Mice

et al. 1999

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Background-The effects of probucol and a phytosterol mixture (FCP-3PI) on atherosclerotic lesion formation, plasma lipoproteins, hepatic and lipoprotein lipase activities, antioxidant enzyme activities, and plasma fibrinogen were investigated in apolipoprotein E-knockout (apoE-KO) mice. Methods and Results-Three groups of 8 mice were fed a diet containing 9% (wt/wt) fat (controls) or the foregoing diet supplemented with either 1% (wt/wt) probucol (the probucol group) or 2% (wt/wt) FCP-3PI (the FCP-3PI group) for 20 weeks. Compared with controls, atherosclerotic lesion size was 3 times greater in the probucol group, whereas it was decreased by half in the FCP-3PI group. Probucol treatment resulted in high plasma probucol concentrations, which correlated (rϭ0.69) with the lesion area. HDL cholesterol was reduced (Ͼ75%) in the probucol group and slightly increased (14%) in the FCP-3PI-treated group. Postheparin lipoprotein lipase (LPL) activity was significantly reduced in both treatment groups, but only FCP-3PI significantly decreased hepatic lipase activity. Plasma fibrinogen was increased 42% by probucol and decreased 19% by FCP-3PI relative to controls. Probucol significantly increased plasma glutathione reductase, glutathione peroxidase, and superoxide dismutase activities (PϽ0.05). In contrast to findings in apoE-KO mice, there was no probucol-induced atherosclerosis in their wild-type counterparts fed the same dose for the same period of time. Conclusions-Antiatherogenic activity of FCP-3PI in apoE-KO mice is associated with an increase in HDL cholesterol concentration along with decreases in hepatic lipase activity and plasma fibrinogen concentrations. Proatherogenic effects of probucol may be related to increased plasma fibrinogen, decreased HDL cholesterol concentrations along with decreased LPL activity, or its direct "toxicity" due to very high plasma concentration. Our studies demonstrate that the antioxidant and cholesterol-lowering properties of probucol do not prevent atherogenesis in this particular animal model.

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Section: Discussionmentioning

confidence: 99%