logging in or signing up HDL PBV1984 Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 1089 Category: Education License: All Rights Reserved Like it (4) Dislike it (1) Added: June 14, 2010 This Presentation is Public Favorites: 2 Presentation Description HDL FOCUS Comments Posting comment... By: jacha (7 month(s) ago) Good presentation, facilitates knowledge of action rather hdl, can you please e mail the ppt at j.acha.perez@gmail.com thanks Saving..... Post Reply Close Saving..... Edit Comment Close By: ranga676 (14 month(s) ago) spectacular presentation...can you please send it to ranga676@gmail.com?? thanks in advance!!!!!!!!! Saving..... Post Reply Close Saving..... Edit Comment Close By: anet21frank (15 month(s) ago) Very good presentation can you please e mail the ppt at anet21frank@gmail.com thanks Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript Focus on High Density Lipoproteins : Focus on High Density Lipoproteins Lipoprotein Classes and Atherosclerosis : Lipoprotein Classes and Atherosclerosis Chylomicrons, VLDL, and their catabolic remnants LDL HDL Pro-atherogenic Anti-atherogenic Slide 3: Introduction High-density lipoprotein (HDL) is one of the five major groups of lipoproteins that enables lipids like cholesterol and triglycerides to be transported within the water based blood stream. HDL can remove cholesterol from atheroma within arteries and transport it back to the liver for excretion or re-utilization. Therefore HDL is also called as good cholesterol. Structure of HDL : Structure of HDL HDL is the smallest of the lipoprotein particles. HDL particles have a size of 6-12.5 nanometers They have high density ~1.12 mainly because of high proportion of proteins HDL Structure : HDL Structure HDL contains approximately 55% protein 3-15% triglycerides 26-46% phospholipids 15-30% cholesteryl esters 2-10% cholesterol. HDL Structure : HDL Structure HDL contains several types of apolipoproteins including: apo-AI Apo-AII apo-CI apo-CII apo-D apo-E. Their most abundant apolipoproteins are apo A-I and apo A-II. HDL Structure : HDL Structure HDL-C HDL Structure : HDL Structure HDL Structure : HDL Structure Alpha HDL Buoyancy : Alpha HDL Buoyancy HDL Synthesis : HDL Synthesis Synthesis of new high-density lipoprotein (HDL) particles begins with the secretion of apolipoprotein A-I (apo A-I) from the liver. The resulting HDL2 (larger, less dense particles) and HDL3 (smaller, more dense particles) can serve as acceptors for ABCG1-mediated cholesterol efflux26. Slide 12: Reverse Cholesterol Transport: Cellular level Slide 13: Role of HDL in lipid redistribuion Role of high-density lipoprotein (HDL) in the redistribution of lipids from cells with excess cholesterol to cells requiring cholesterol or to the liver for excretion. The reverse cholesterol transport pathway is indicated by arrows (net transfer of cholesterol from cells ➙ HDL ➙ LDL ➙ liver). Slide 14: Reverse Cholesterol Transport: Cellular level Several steps in the metabolism of HDL can contribute to the transport of cholesterol from lipid laden macrophages of atherosclerotic arteries, termed foam cells to the liver for secretion into the bile. This pathway has been termed reverse cholesterol transport and is considered as the classical protective function of HDL towards atherosclerosis. Slide 15: Reverse Cholesterol Transport: Cellular level High-density lipoprotein (HDL) cholesterol promotes and facilitates the process of reverse cholesterol transport (RCT), whereby excess macrophage cholesterol is effluxed to HDL and ultimately returned to the liver for excretion. Efflux to nascent and mature HDL occurs via the transporters ABCA1 and ABCG1, respectively. The HDL cholesterol is returned to the liver via the hepatic receptor SR-BI or by transfer to apolipoprotein (apo) B–containing lipoproteins by the action of cholesteryl ester transfer protein (2). Slide 16: HDL metabolism and reverse cholesterol transport Role of Hepatic Lipase and Lipoprotein Lipase in HDL Metabolism : Role of Hepatic Lipase and Lipoprotein Lipase in HDL Metabolism CM = chylomicron; CMR = chylomicron remnant; HDL = high-density lipoprotein; HL = hepatic lipase; IDL = intermediate-density lipoprotein; LPL = lipoprotein lipase; PL = phospholipase; TG = triglyceride B Kidney Endothelium B TG CMR/IDL C-II CM/VLDL HL LPL A-I CE TG HDL2 PL A-I CE HDL3 PL Phospholipids and apolipoproteins HDL Metabolism in CETP Deficiency : HDL Metabolism in CETP Deficiency A-I CE FC FC LCAT A-I Macrophage B Delayed catabolism CETP ABC1 HDL VLDL/LDL Nascent HDL CE Targeting HDL Metabolism : Targeting HDL Metabolism Improve HDL function apoAI Milano apoAI mimetic peptides Increase HDL synth. or infuse rHDL apoM? ETC216 LPL LUV’s apoAI Delipidated HDL Extend/reduce circulation Time Block clearance trimeric apoAI SR-BI Modulate PL phosphatidyl inositol sPLA2 Improve lipidation maturation ABCA1 ABCG1 LCAT HDL remodeling HL, EL, PLTP? apoCI? CETP PL,FC,CE,apo’s Renal clearance CETP Inhibition and Lipoprotein Metabolism : CETP Inhibition and Lipoprotein Metabolism Slide 21: Cholesterol efflux and reverse cholesterol transport is modulated by two receptors HDL-C Protection Against Atherosclerosis : HDL-C Protection Against Atherosclerosis Acts by inhibiting Oxidation Inflammation Activation of endothelium Coagulation Platelet aggregation Inhibitory properties of HDL : Inhibitory properties of HDL Slide 24: HDL-C: Anti-atherogenic effects HDL inhibits expression of adhesion molecules HDL inhibitsoxidationof LDL HDL promotes cholesterol efflux HDL activates eNOS LDL LDL Endothelium Vessel Lumen Monocyte Modified LDL Macrophage MCP-1 AdhesionMolecules Cytokines Intima Foam Cell NO NO NO NO RCT Slide 25: HDL metabolism: 5 key genes Slide 26: HDL: Apo AI-rich particles Slide 27: Anti-inflammatory effects of HDL Slide 28: Antioxidant Action of HDL cholesterol Antioxidant Action of HDL cholesterol : Antioxidant Action of HDL cholesterol Slide 30: LDL LDL Miyazaki A et al. Biochim Biophys Acta 1992;1126:73-80. Endothelium Vessel Lumen Monocyte Modified LDL Macrophage MCP-1 AdhesionMolecules Cytokines HDL Prevents Formation of Foam Cells Intima HDL Promote Cholesterol Efflux Foam Cell Slide 31: LDL LDL Cockerill GW et al. Arterioscler Thromb Vasc Biol 1995;15:1987-1994. Endothelium Vessel Lumen Monocyte Modified LDL Macrophage MCP-1 AdhesionMolecules Cytokines Inhibition of Adhesion Molecules Intima HDL InhibitOxidationof LDL HDL Inhibit Adhesion Molecule Expression Foam Cell HDL Promote Cholesterol Efflux Slide 32: LDL LDL Mackness MI et al. Biochem J 1993;294:829-834. Endothelium Vessel Lumen Monocyte Modified LDL Macrophage MCP-1 AdhesionMolecules Cytokines HDL Inhibits the Oxidative Modification of LDL Foam Cell HDL Promote Cholesterol Efflux Intima HDL InhibitOxidationof LDL Additional Anti-inflammatory Properties of HDL : Additional Anti-inflammatory Properties of HDL HDL bind and neutralizes proinflammatory lipopolysaccharides The acute phase reactant SAA binds to plasma HDL, which possibly neutralizes the effects of SAA 1. Baumberger C et al. Pathobiology 1991;59:378-383. 2. Benditt EP et al. Proc Natl Acad Sci U S A 1977;74:4025-4028 Slide 34: Apo A-I protects against atherosclerosis Recommended range of HDL : Recommended range of HDL The American Heart Association, NIH and NCEP provides a set of guidelines for fasting HDL levels Slide 36: Relationship between HDL cholesterol and CHD events. Data from the Framingham Study Risk of CHD Castelli WP. Can J Cardiol. 1988;4(suppl A):5A-10A. 3 2 1 4 Major cardiovascular event frequency by LDL-C and HDL-C levels in TNT study : Major cardiovascular event frequency by LDL-C and HDL-C levels in TNT study Causes of Low HDL : Causes of Low HDL Steps to Improve HDL Level : Steps to Improve HDL Level Life style modifications Exercise Alcohol Smoking cessation Drugs Niacin Fibrates Statins CETP inhibitors ApoA-1 Milano/ApoA-1mimetic HDL-C levels are modifiable by the quantity and quality of exercise : HDL-C levels are modifiable by the quantity and quality of exercise HERITAGE STUDY: Effects of 20 wks of endurance exercise training on lipid profile : HERITAGE STUDY: Effects of 20 wks of endurance exercise training on lipid profile Smoking cessation increases only HDL-C, but not TC,LDL-C or TG : Smoking cessation increases only HDL-C, but not TC,LDL-C or TG Slide 43: Mechanism of action of nicotinic acid Slide 44: Fenofibrate & gemfibrozil are derivatives of fibric acid that lower TGs and increase HDL levels. Fenofibrate is more effective at lowering LDL & TGs. Fibrates Slide 45: Mechanism of Action of Fenofibrate Statin drugs are structural analogs of HMG-CoA : Statin drugs are structural analogs of HMG-CoA Slide 47: Statin Evidence: Landmark Statin Trials Slide 48: Statin Evidence: Expanding Benefits Statin Evidence: Benefits : Statin Evidence: Benefits The statin trials have demonstrated significant decreases in CVD morbidity and mortality. Reduction in CVD events has been demonstrated in patients with stable CHD as well as acute coronary syndrome patients. Additionally, lowering LDL-C to target levels has beneficial effects in patients with normal or moderately elevated LDL-C. Statin Efficacy: Lipid Lowering : Drug Class LDL-C HDL-C Triglycerides Statins* 18% to 60% 5% to 15% 7% to 37% Bile Acid 15% to 30% 3% to 5% No change orSequestrants increase Nicotinic Acid 5% to 25% 15% to 35% 20% to 50% Fibric Acids 5% to 20% 10% to 20% 20% to 50% Statin Efficacy: Lipid Lowering Adapted from NCEP Expert Panel. JAMA. 2001;285:2486-2497. v v v v v v v v v v v Slide 51: Statin Efficacy: ACCESS Disclaimer : Disclaimer The data, images, graphs and tables provided in this presentation has been developed by clinicians and medical writers. It has also been validated by experts. Although great care has been taken in compiling checking the information, the authors, BioQuest and its servants or agents, and sponsors shall not be responsible or in anyway, liable for any errors, omissions on inaccuracies in the publication whether arising from negligence or otherwise however, or for any consequences arising there from. The inclusion or exclusion of any product does not mean that the publisher advocates or rejects its use either generally or in any particular field or fields. The data, images and illustrations are provided in their original form. Wherever applicable, the relevant sources and the details of the original copyright owners are provided for the reference of the readers. Should you wish to recreate the data, images, graphs and tables, you are advised to contact the respective authors or service providers wherever necessary. USV or BioQuest will not be liable for any consequences arising from the unauthorized usage of this data. You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.
HDL PBV1984 Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 1089 Category: Education License: All Rights Reserved Like it (4) Dislike it (1) Added: June 14, 2010 This Presentation is Public Favorites: 2 Presentation Description HDL FOCUS Comments Posting comment... By: jacha (7 month(s) ago) Good presentation, facilitates knowledge of action rather hdl, can you please e mail the ppt at j.acha.perez@gmail.com thanks Saving..... Post Reply Close Saving..... Edit Comment Close By: ranga676 (14 month(s) ago) spectacular presentation...can you please send it to ranga676@gmail.com?? thanks in advance!!!!!!!!! Saving..... Post Reply Close Saving..... Edit Comment Close By: anet21frank (15 month(s) ago) Very good presentation can you please e mail the ppt at anet21frank@gmail.com thanks Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript Focus on High Density Lipoproteins : Focus on High Density Lipoproteins Lipoprotein Classes and Atherosclerosis : Lipoprotein Classes and Atherosclerosis Chylomicrons, VLDL, and their catabolic remnants LDL HDL Pro-atherogenic Anti-atherogenic Slide 3: Introduction High-density lipoprotein (HDL) is one of the five major groups of lipoproteins that enables lipids like cholesterol and triglycerides to be transported within the water based blood stream. HDL can remove cholesterol from atheroma within arteries and transport it back to the liver for excretion or re-utilization. Therefore HDL is also called as good cholesterol. Structure of HDL : Structure of HDL HDL is the smallest of the lipoprotein particles. HDL particles have a size of 6-12.5 nanometers They have high density ~1.12 mainly because of high proportion of proteins HDL Structure : HDL Structure HDL contains approximately 55% protein 3-15% triglycerides 26-46% phospholipids 15-30% cholesteryl esters 2-10% cholesterol. HDL Structure : HDL Structure HDL contains several types of apolipoproteins including: apo-AI Apo-AII apo-CI apo-CII apo-D apo-E. Their most abundant apolipoproteins are apo A-I and apo A-II. HDL Structure : HDL Structure HDL-C HDL Structure : HDL Structure HDL Structure : HDL Structure Alpha HDL Buoyancy : Alpha HDL Buoyancy HDL Synthesis : HDL Synthesis Synthesis of new high-density lipoprotein (HDL) particles begins with the secretion of apolipoprotein A-I (apo A-I) from the liver. The resulting HDL2 (larger, less dense particles) and HDL3 (smaller, more dense particles) can serve as acceptors for ABCG1-mediated cholesterol efflux26. Slide 12: Reverse Cholesterol Transport: Cellular level Slide 13: Role of HDL in lipid redistribuion Role of high-density lipoprotein (HDL) in the redistribution of lipids from cells with excess cholesterol to cells requiring cholesterol or to the liver for excretion. The reverse cholesterol transport pathway is indicated by arrows (net transfer of cholesterol from cells ➙ HDL ➙ LDL ➙ liver). Slide 14: Reverse Cholesterol Transport: Cellular level Several steps in the metabolism of HDL can contribute to the transport of cholesterol from lipid laden macrophages of atherosclerotic arteries, termed foam cells to the liver for secretion into the bile. This pathway has been termed reverse cholesterol transport and is considered as the classical protective function of HDL towards atherosclerosis. Slide 15: Reverse Cholesterol Transport: Cellular level High-density lipoprotein (HDL) cholesterol promotes and facilitates the process of reverse cholesterol transport (RCT), whereby excess macrophage cholesterol is effluxed to HDL and ultimately returned to the liver for excretion. Efflux to nascent and mature HDL occurs via the transporters ABCA1 and ABCG1, respectively. The HDL cholesterol is returned to the liver via the hepatic receptor SR-BI or by transfer to apolipoprotein (apo) B–containing lipoproteins by the action of cholesteryl ester transfer protein (2). Slide 16: HDL metabolism and reverse cholesterol transport Role of Hepatic Lipase and Lipoprotein Lipase in HDL Metabolism : Role of Hepatic Lipase and Lipoprotein Lipase in HDL Metabolism CM = chylomicron; CMR = chylomicron remnant; HDL = high-density lipoprotein; HL = hepatic lipase; IDL = intermediate-density lipoprotein; LPL = lipoprotein lipase; PL = phospholipase; TG = triglyceride B Kidney Endothelium B TG CMR/IDL C-II CM/VLDL HL LPL A-I CE TG HDL2 PL A-I CE HDL3 PL Phospholipids and apolipoproteins HDL Metabolism in CETP Deficiency : HDL Metabolism in CETP Deficiency A-I CE FC FC LCAT A-I Macrophage B Delayed catabolism CETP ABC1 HDL VLDL/LDL Nascent HDL CE Targeting HDL Metabolism : Targeting HDL Metabolism Improve HDL function apoAI Milano apoAI mimetic peptides Increase HDL synth. or infuse rHDL apoM? ETC216 LPL LUV’s apoAI Delipidated HDL Extend/reduce circulation Time Block clearance trimeric apoAI SR-BI Modulate PL phosphatidyl inositol sPLA2 Improve lipidation maturation ABCA1 ABCG1 LCAT HDL remodeling HL, EL, PLTP? apoCI? CETP PL,FC,CE,apo’s Renal clearance CETP Inhibition and Lipoprotein Metabolism : CETP Inhibition and Lipoprotein Metabolism Slide 21: Cholesterol efflux and reverse cholesterol transport is modulated by two receptors HDL-C Protection Against Atherosclerosis : HDL-C Protection Against Atherosclerosis Acts by inhibiting Oxidation Inflammation Activation of endothelium Coagulation Platelet aggregation Inhibitory properties of HDL : Inhibitory properties of HDL Slide 24: HDL-C: Anti-atherogenic effects HDL inhibits expression of adhesion molecules HDL inhibitsoxidationof LDL HDL promotes cholesterol efflux HDL activates eNOS LDL LDL Endothelium Vessel Lumen Monocyte Modified LDL Macrophage MCP-1 AdhesionMolecules Cytokines Intima Foam Cell NO NO NO NO RCT Slide 25: HDL metabolism: 5 key genes Slide 26: HDL: Apo AI-rich particles Slide 27: Anti-inflammatory effects of HDL Slide 28: Antioxidant Action of HDL cholesterol Antioxidant Action of HDL cholesterol : Antioxidant Action of HDL cholesterol Slide 30: LDL LDL Miyazaki A et al. Biochim Biophys Acta 1992;1126:73-80. Endothelium Vessel Lumen Monocyte Modified LDL Macrophage MCP-1 AdhesionMolecules Cytokines HDL Prevents Formation of Foam Cells Intima HDL Promote Cholesterol Efflux Foam Cell Slide 31: LDL LDL Cockerill GW et al. Arterioscler Thromb Vasc Biol 1995;15:1987-1994. Endothelium Vessel Lumen Monocyte Modified LDL Macrophage MCP-1 AdhesionMolecules Cytokines Inhibition of Adhesion Molecules Intima HDL InhibitOxidationof LDL HDL Inhibit Adhesion Molecule Expression Foam Cell HDL Promote Cholesterol Efflux Slide 32: LDL LDL Mackness MI et al. Biochem J 1993;294:829-834. Endothelium Vessel Lumen Monocyte Modified LDL Macrophage MCP-1 AdhesionMolecules Cytokines HDL Inhibits the Oxidative Modification of LDL Foam Cell HDL Promote Cholesterol Efflux Intima HDL InhibitOxidationof LDL Additional Anti-inflammatory Properties of HDL : Additional Anti-inflammatory Properties of HDL HDL bind and neutralizes proinflammatory lipopolysaccharides The acute phase reactant SAA binds to plasma HDL, which possibly neutralizes the effects of SAA 1. Baumberger C et al. Pathobiology 1991;59:378-383. 2. Benditt EP et al. Proc Natl Acad Sci U S A 1977;74:4025-4028 Slide 34: Apo A-I protects against atherosclerosis Recommended range of HDL : Recommended range of HDL The American Heart Association, NIH and NCEP provides a set of guidelines for fasting HDL levels Slide 36: Relationship between HDL cholesterol and CHD events. Data from the Framingham Study Risk of CHD Castelli WP. Can J Cardiol. 1988;4(suppl A):5A-10A. 3 2 1 4 Major cardiovascular event frequency by LDL-C and HDL-C levels in TNT study : Major cardiovascular event frequency by LDL-C and HDL-C levels in TNT study Causes of Low HDL : Causes of Low HDL Steps to Improve HDL Level : Steps to Improve HDL Level Life style modifications Exercise Alcohol Smoking cessation Drugs Niacin Fibrates Statins CETP inhibitors ApoA-1 Milano/ApoA-1mimetic HDL-C levels are modifiable by the quantity and quality of exercise : HDL-C levels are modifiable by the quantity and quality of exercise HERITAGE STUDY: Effects of 20 wks of endurance exercise training on lipid profile : HERITAGE STUDY: Effects of 20 wks of endurance exercise training on lipid profile Smoking cessation increases only HDL-C, but not TC,LDL-C or TG : Smoking cessation increases only HDL-C, but not TC,LDL-C or TG Slide 43: Mechanism of action of nicotinic acid Slide 44: Fenofibrate & gemfibrozil are derivatives of fibric acid that lower TGs and increase HDL levels. Fenofibrate is more effective at lowering LDL & TGs. Fibrates Slide 45: Mechanism of Action of Fenofibrate Statin drugs are structural analogs of HMG-CoA : Statin drugs are structural analogs of HMG-CoA Slide 47: Statin Evidence: Landmark Statin Trials Slide 48: Statin Evidence: Expanding Benefits Statin Evidence: Benefits : Statin Evidence: Benefits The statin trials have demonstrated significant decreases in CVD morbidity and mortality. Reduction in CVD events has been demonstrated in patients with stable CHD as well as acute coronary syndrome patients. Additionally, lowering LDL-C to target levels has beneficial effects in patients with normal or moderately elevated LDL-C. Statin Efficacy: Lipid Lowering : Drug Class LDL-C HDL-C Triglycerides Statins* 18% to 60% 5% to 15% 7% to 37% Bile Acid 15% to 30% 3% to 5% No change orSequestrants increase Nicotinic Acid 5% to 25% 15% to 35% 20% to 50% Fibric Acids 5% to 20% 10% to 20% 20% to 50% Statin Efficacy: Lipid Lowering Adapted from NCEP Expert Panel. JAMA. 2001;285:2486-2497. v v v v v v v v v v v Slide 51: Statin Efficacy: ACCESS Disclaimer : Disclaimer The data, images, graphs and tables provided in this presentation has been developed by clinicians and medical writers. It has also been validated by experts. Although great care has been taken in compiling checking the information, the authors, BioQuest and its servants or agents, and sponsors shall not be responsible or in anyway, liable for any errors, omissions on inaccuracies in the publication whether arising from negligence or otherwise however, or for any consequences arising there from. The inclusion or exclusion of any product does not mean that the publisher advocates or rejects its use either generally or in any particular field or fields. The data, images and illustrations are provided in their original form. Wherever applicable, the relevant sources and the details of the original copyright owners are provided for the reference of the readers. Should you wish to recreate the data, images, graphs and tables, you are advised to contact the respective authors or service providers wherever necessary. USV or BioQuest will not be liable for any consequences arising from the unauthorized usage of this data.