New Therapeutic Approaches to the Treatment of Dyslipidemia Daniel J. Rader  Cell Metabolism  Volume 23, Issue 3, Pages 405-412 (March 2016) DOI: 10.1016/j.cmet.2016.01.005 Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 1 Mechanisms of LDL-Lowering Therapies Statins, the cholesterol absorption inhibitor (CAI) ezetimibe, and bile acid sequestrants (BAS) all reduce hepatocyte cholesterol, leading to transcriptional upregulation of the LDL receptor (LDLR). PCSK9 inhibitors prevent PCSK9-mediated degradation of the LDLR and post-translationally increase its presence on the hepatocyte cell surface. The inhibitor of microsomal triglyceride transfer protein (MTP) lomitapide and the antisense oligonucleotide (ASO) to apoB mipomersen both reduce VLDL assembly and secretion, thus reducing LDL-C levels in an LDLR-independent manner. Cell Metabolism 2016 23, 405-412DOI: (10.1016/j.cmet.2016.01.005) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 2 Proteins Regulating Lipoprotein Lipase Activity Are Therapeutic Targets ApoC-III, ANGPTL3, and ANGPTL4 are all inhibitors of LPL activity and thus candidates for therapeutic inhibition. ApoA-V is a stimulator of LPL activity and thus a candidate for upregulation or augmenting its activity. Cell Metabolism 2016 23, 405-412DOI: (10.1016/j.cmet.2016.01.005) Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 3 The Reverse Cholesterol Transport Pathway from Macrophages to Liver CETP inhibitors raise HDL-C levels by blocking the transport of cholesteryl esters (CE) out of HDL to apoB-lipoproteins. Infusion of recombinant HDL (rHDL) or recombinant LCAT (rLCAT) have the potential to promote macrophage cholesterol efflux and reverse cholesterol transport. Cell Metabolism 2016 23, 405-412DOI: (10.1016/j.cmet.2016.01.005) Copyright © 2016 Elsevier Inc. Terms and Conditions