Overview Lipoprotein metabolism Digestive lipid metabolism Cholesterol balance Drugs affecting cholesterol metabolism

Statins Inhibit biosynthesis of cholesterol Lower LDL cholesterol Mechanism: Promote LDL clearance

Statins LDL Receptor Acetate HMG-CoA Reductase Cholesterol

Statins LDL Receptor Acetate HMG-CoA Reductase Cholesterol LDL

Bile Salt Sequestrants Promote loss of bile salts from the enterohepatic circulation Lower LDL cholesterol Mechanism: Promote LDL clearance

Bile Salt Sequestrants Cholesterol Phospholipid

Bile Salt Sequestrants and the Enterohepatic Circulation Duodenum Biliary Transport and Storage Jejunum Ileum Fecal Excretion Colon

Bile Salt Sequestrants LDL Receptor Cholesterol LDL

PCSK9 Inhibitors Prevent PCSK9-mediated degradation of LDL receptors Lower LDL cholesterol Mechanism: Promote LDL clearance

Liver Cell or other Cell Type PCSK9 Inhibitors LDL Receptor Liver Cell or other Cell Type X PSCK9

Liver Cell or other Cell Type PCSK9 Inhibitors LDL Receptor Liver Cell or other Cell Type LDL

Cholesterol Absorption Inhibitors Inhibit absorption of dietary cholesterol Inhibit reabsorption of biliary cholesterol Lower LDL cholesterol Mechanism : Inhibit LDL formation

Cholesterol Absorption Inhibitors Plant sterols and stanols Ezetimibe

Cholesterol Absorption LYMPH ENTEROCYTE INTESTINAL LUMEN Cholesterol NPC1L1 ACAT Cholesteryl Ester ABCG5/G8

Cholesterol Absorption Inhibitors Plant sterols and stanols Ezetimibe

Plant Sterols and Stanols Dietary Cholesterol Sterol/Stanol Free Cholesterol

Plant Sterols and Stanols Dietary Cholesterol Sterol/Stanol Free Cholesterol

Plant Sterols and Stanols LYMPH ENTEROCYTE INTESTINAL LUMEN Cholesterol NPC1L1 ACAT Cholesteryl Ester ABCG5/G8

Plant Sterols and Stanols LYMPH ENTEROCYTE INTESTINAL LUMEN Cholesterol NPC1L1 ACAT Cholesteryl Ester ABCG5/G8

Plant Sterols and Stanols LYMPH ENTEROCYTE INTESTINAL LUMEN Cholesterol NPC1L1 ACAT Cholesteryl Ester ABCG5/G8

Cholesterol Absorption Inhibitors Plant sterols and stanols Ezetimibe

X Ezetimibe LYMPH ENTEROCYTE INTESTINAL LUMEN Cholesterol Cholesteryl NPC1L1 ACAT Cholesteryl Ester ABCG5/G8

X Ezetimibe LYMPH ENTEROCYTE INTESTINAL LUMEN Cholesterol Cholesteryl NPC1L1 ACAT Cholesteryl Ester ABCG5/G8

Cholesterol Absorption Inhibitors LYMPH ENTEROCYTE INTESTINAL LUMEN CM apoB48 Triglyceride Cholesteryl Ester

Cholesterol Absorption Inhibitors LYMPH ENTEROCYTE INTESTINAL LUMEN CM apoB48 Triglyceride Cholesteryl Ester

Cholesterol Absorption Inhibitors LYMPH ENTEROCYTE INTESTINAL LUMEN CM apoB48 Triglyceride Cholesteryl Ester

Cholesterol Absorption Inhibitors LDL apoB100 Liver Duodenum VLDL apoB100 Jejunum Ileum X CM Remnant apoB48 CM apoB48 Colon

Mipomersen and Lomitapide Inhibit apoB synthesis (mipomersen) Inhibit MTP activity (lomitapide) Mechanism : Inhibit LDL formation

Mipomersen and Lomitapide X X MTP MTP ApoB Triglyceride secretion Hepatic Steatosis

Niacin Lowers LDL cholesterol by inhibiting VLDL production Increases HDL cholesterol

Niacin Inhibits VLDL Production Presence of Triglycerides MTP MTP ApoB Absence of Triglycerides Degradation of apoB ApoB

Niacin Promotes Reverse Cholesterol Transport LCAT Cholesterol HDL3 Phospholipid pre-ß-HDL apoA-I ABCA1 Selective Lipid Uptake Cholesterol LCAT CETP BILE HDL2 SR-BI PERIPHERAL TISSUES LIVER BLOOD

Fibrates Decrease trigylceride-rich lipoproteins (VLDL) HDL: Decrease when baseline levels are high Increase when baseline levels are low

Mechanisms of Fibrate Actions Increase activity of lipoprotein lipase Decrease hepatic triglyceride production Increase affinity of LDL for the LDL receptor Increased HDL production, due to increase apoA-I synthesis

Overview Lipoprotein metabolism Digestive lipid metabolism Cholesterol balance Drugs affecting cholesterol metabolism