Summary
Pharmacological intervention for altering plasma levels of lipoproteins is usually aimed at reducing atherogenesis and preventing coronary heart disease (CHD). Drug therapy should be attempted only after other nonpharmacological methods (such as elimination of smoking, weight reduction and exercise) have been tried.
An overview of the metabolism of low density lipoprotein (LDL) and high density lipoprotein (HDL) particles is the basis of this paper. Various sites suitable for pharmacological intervention are identified. LDL metabolism can be altered at 2 potential sites, with a consequent reduction in the plasma level of this atherogenic lipoprotein. Hydroxymethylglutaryl coenzyme A (HMO CoA) reductase inhibitors (such as lovastatin) and cation-exchange resins (e.g. cholestyramine) reduce LDL levels by stimulating the hepatic synthesis of apolipoprotein (apo) B,E receptors. Very low density lipoprotein (VLDL) secretion is inhibited by nicotinic acid (niacin) and gemfibrozil, leading to a secondary decrease in LDL production from VLDL. Probucol also reduces the LDL concentration and inhibits the oxidative modification of LDL. Gemfibrozil and other fibrates stimulate lipoprotein lipase activity, thereby decreasing VLDL concentration.
Reduction of the LDL concentration is effective in reducing CHD incidence, whether this is achieved by stimulation of catabolism or inhibition of production of the lipoprotein.
In contrast, the mechanism of raising plasma HDL-cholesterol levels is probably relevant to the potential clinical benefits associated with drug therapy. Gemfibrozil and cholestyramine stimulate synthesis of apoprotein A1, the major protein constituent of HDL particles. Both drugs have been shown to reduce the incidence of CHD in clinical trials, via mechanisms that are related in part to their HDL-raising activity. Gemfibrozil and other fibrates also raise HDL-cholesterol via stimulation of lipoprotein lipase, and nicotinic acid does so by reducing HDL catabolism.
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Miller, N.E. Pharmacological Intervention for Altering Lipid Metabolism. Drugs 40 (Suppl 1), 26–32 (1990). https://doi.org/10.2165/00003495-199000401-00007
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DOI: https://doi.org/10.2165/00003495-199000401-00007