MTP inhibitors and ACAT inhibitors. An update

Currently, statin therapy is the first-line treatment for patients with hypercholesterolemia, although their effects on plasma triglyceride(TG) levels are modest and variable. Inhibition of microsomal triglyceride transfer protein(MTP), a key protein involved in the assembly of the apoB-containing lipoproteins, is an attractive lipid-lowering strategy. In animal models, MTP inhibitors have dramatic effects not only on plasma cholesterol and LDL levels but on TG levels as well, offering the potential for greater efficacy and plasma lipid control in both hypertriglyceridemia and mixed hyperlipidemia. Inhibitors of acyl-CoA: cholesterol acyltransferase(ACAT) present another strategy in treating atherosclerosis through direct inhibition of ACAT in macrophages of the arterial wall. Recent studies in mouse models of atherosclerosis lacking ACAT1, however, may argue against the selective inhibition of macrophage ACAT1.