Abstract
The stimulation of reverse cholesterol transport (RCT) is important for the prevension and regression of atherosclerosis. The high concentration of plasma HDL and high activity of LCAT seem to stimulate RCT. Esterified cholesterol (EC), produced by LCAT reaction in HDL is transfered directly to the liverr or to VLDL, IDL and LDL by lipid transfer protein (LTP). It is not well defined whether or not the high activity of LTP stimulates RCT. The activities of LCAT and LTP in CHD were assayed first in order to determine their role in atherosclerosis, and the effects of probucol and pravastatin on their activities were estimated for studying the effects of those drugs on reverse cholesterol transport.
Plasma TC, TG and apo B levels were high, and HDL-C and apo AI levels were low in CHD patients as is well known. LCAT activities were significantly higher in CHD than in control subjects but were slightly lower in CHD patients without hyperlipoproteinemia. The activities of LTP were 84±44units (mean±SD; the value of pooled control plasma: 100units) in control subjects and 118±54units in CHD patients. LTP activities were significantly higher in CHD than in control subjects (P<0.05). Plasma lipids level did not affect the correlation.
Probucol reduced plasma TC by 19% and HDL-C by 15% significantly by 12 weeks of treatment, Pravastatin significantly reduced plasma TC by 15% and increased plasma HDL-C by 9% without statistical significance. LCAT activities were 105±18n mol/ml/hr and 87±21n mol/ml/ hr before and after 12 weeks of probucol treatment and were 104±16n mol/ml/hr and 90±20n mol/ ml/hr before and after 12 weeks of pravastatin treatment. The decreases of LCAT activity by probucol and pravastatin were not statistically significant. Probucol significantly increased LTP activity by 26%. Pravastatin tended to decrease LTP activity by 46% without statistical significance.
LCAT activity is affected by plasma lipids levels. Therefore, LCAT activity must be low in CHD when plasma lipids levels are matched. As determined from the results in CHD, the high plasma HDL levels, high LCAT activity and low LTP activity stimulate RCT and prevent atherosclerosis. Probucol reduced plasma HDL levels and increased LTP activity significantly and tended to decrease LCAT activity. Therefore, probucol may inhibit RCT. Pravastatin tended to increase plasma HDL levels and to decrease LTP activity, hence, pravastatin may stimulate RCT. The effects not only on the metabolism of atherogenic lipoproteins but also on RCT must be carefully investigated for the treatment of hyperlipoproteinemia.
