,Drug targets beyond HMG-CoA reductase: Why venture beyond the statins?

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In this review, we aim to convey a brief, select history of the development of cholesterol-lowering therapies.We focus particularly on the highly successful statins as well as setbacks that should serve as cautionary tales. We go on to preview recent developments that may complement, if not one day replace, the statins. Our focus is on pharmacological interventions, particularly those targeting the cholesterol biosynthetic pathway. Also, we examine therapies under current investigation that target the assembly of atherogenic lipoproteins (via apolipoprotein B or microsomal triglyceride transfer protein), the stability of the Iow-density lipoprotein-receptor (via PCSK9, proprotein convertase subtilisin kexin 9), or are designed to increase high-density lipoprotein-cholesterol (via inhibition of cholesteryl ester transfer protein).
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