HIGHER PLASMA-LIPID TRANSFER PROTEIN ACTIVITIES AND UNFAVORABLE LIPOPROTEIN CHANGES IN CIGARETTE-SMOKING MEN

The mechanisms responsible for the atherogenic lipoprotein changes associated with cigarette smoking are largely unknown. Lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) are key factors in the esterification of plasma cholesterol and the transfer of cholesteryl ester from high-density lipoproteins (HDLs) toward very-low- and low-density lipoproteins (VLDLs + LDLs). Another transfer factor, phospholipid transfer protein (PLTP), recently has been shown to be involved in the interconversion of HDL particles in vitro, but its physiological function is not yet clear. We measured the activities of LCAT, CETP (as cholesteryl ester exchange activity), and PLTP using exogenous substrate assays as well as lipoprotein profiles in the plasma of 21 normolipidemic cigarette-smoking men (total plasma cholesterol below 6.5 mmol/L and triglyceride below 2.5 mmol/L) and 21 individually matched nonsmoking control subjects. HDL cholesterol, HDL cholesteryl ester, and plasma apolipoprotein A-I levels were lower in the smokers than in the control subjects (p less than or equal to .05 for all parameters). Median plasma CETP activity was 18% higher (P <.02) and median plasma PLTP activity was 8% higher (P <.05) in the smokers compared with the nonsmokers. LCAT activity was not different between the groups. HDL cholesteryl ester concentration was positively related to LCAT activity in control subjects but not in smokers. By contrast, there was an inverse relation of CETP activity with HDL cholesteryl ester in smokers but not in nonsmokers. Multiple regression analysis demonstrated that the lowering effect of smoking on HDL cholesteryl ester could be explained by its influence on CETP activity. In both groups VLDL + LDL cholesteryl ester levels were positively related to CETP activity as well as to PLTP activity. Thus, the higher the levels of CETP and PLTP activity in smokers are, the higher are cholesteryl ester concentrations in VLDL + LDL and the lower in HDL. This case-control study suggests that higher levels of lipid transfer protein activities may provide a mechanism that contributes to unfavorable lipoprotein changes associated with cigarette smoking

Impaired suppression of plasma free fatty acids and triglycerides by acute hyperglycaemia-induced hyperinsulinaemia and alterations in high density lipoproteins in essential hypertension

Objectives. Essential hypertension may be associated with abnormalities in free fatty acids (FFA) and triglyceride metabolism, which could lead to alterations in high density lipoproteins (HDL). Lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) are key factors in the esterification of cholesterol and the subsequent transfer of cholesteryl ester from HDL towards triglyceride-rich lipoproteins. We compared baseline plasma lipids, HDL lipids, plasma LCAT and CETP activity as well as the lowering Of plasma FFA and triglycerides by acute hyperglycaemia-induced hyperinsulinaemia in patients with essential hypertension and control subjects. Setting. University Hospital, Groningen. Subjects and design. Eight patients with essential hypertension and eight control subjects were studied during a 3-h hyperglycaemic glucose clamp (blood glucose, 10 mmol L(-1)). Main outcome measures. Plasma insulin, FFA, triglycerides and HDL lipids, plasma LCAT and CETP. Results. Baseline plasma FFA, total cholesterol and HDL cholesterol were not different between the groups, but plasma triglycerides tended to be higher in the hypertensive patients (P Conclusion. The action of insulin on FFA metabolism is impaired which is likely to contribute to higher plasma triglycerides in essential hypertension. In turn, higher triglycerides influence the HDL lipid composition, either directly or via an effect on the plasma LCAT/CETP ratio