1. HDL and Atherosclerosis

2. Atherosclerosis is a progressive disease
Plaque Rupture/ Fissure & Thrombosis
Unstable
Angina
Occlusive
Atherosclerotic Plaque
Fatty Streak
Fibrous Plaque
Normal MI
Coronary
Death
Atherosclerosis is a progressive disease, typically starting in adolescence and developing over the course of several decades until clinically manifested as heart attack, stroke or peripheral vascular disease (intermittent claudication).
Information on atherosclerosis is available at :
Effort Angina
Claudication
Clinically Silent
Stroke
Critical Leg Ischemia
Increasing Age

3. HDL Subpopulations Particle shape Apolipoprotein composition
Discoidal
Spherical
A-I HDL
A-I/A-II HDL
E HDL
HDL are the smallest and densest of the plasma lipoproteins.
HDL exist in the plasma as a number of subpopulations of particles of varying shape, size, density and composition. The main apolipoproteins in HDL are apolipoprotein (apo)A-I (70%) and apoA-II (20%). HDL also transport additional proteins such as CETP (cholesteryl ester transfer protein), LCAT (lecithin:cholesterol acyltransferase), PLTP (phospholipid transfer protein) and PON( paraoxonase).
Most of the HDL particles in the plasma are spherical. Discoidal HDL particles (nascent HDL) only exist transiently before conversion to spherical HDL particles.
HDL particles carry cholesterol from the body's tissues to the liver for reprocessing or excretion.
Reference
Barter P, Rye K-A. High density cholesterol: the new target. A handbook for clinicians. Sherborne Gibbs, Birmingham, 2007
Lipid-poor apoA-I
Particle size
HDL2b
HDL2a
HDL3a
HDL3b
HDL3c

4. Apolipoproteins Apo-A I carries ”good cholesterol” ( HDL )
Apo B carries ”bad cholesterol” ( LDL )
Apolipoproteins are components of both LDL and HDL.
The main apolipoproteins in HDL are apolipopotein A-I (apoA-I) and apolipoprotein A-II (apoA-II). These comprise about 70% and 20% of the total HDL protein, respectively. Most HDL particles also contain other minor apolipoproteins.

5. Spherical HDL particle
HDL particles consist of a fatty core (mainly cholesteryl esters with a small amount of triglyceride), surrounded by a surface layer of phospholipids, unesterified cholesterol and apolipoproteins.
Reference
Barter P, Rye K-A. High density cholesterol: the new target. A handbook for clinicians. Sherborne Gibbs, Birmingham, 2005

6. CE TG HDL Metabolism Macrophage Bile A-I CE A-I FC LCAT CE ABCA1 SR-BI
HL, EL
PLTP
CETP
LDLR
HDL metabolism is complex and presents a variety of targets for therapeutic intervention. These include:
1. HDL cholesteryl esters may be transferred to very-low-density lipoproteins (VLDL) and low-density lipoprotein (LDL) by CETP (cholesteryl ester transfer protein) and then removed from the plasma as components of these lipoproteins.
2. HDL cholestery esters (CE) may be selectively taken up by the liver in a process involving binding of HDL to SR-B1 (scavenger receptor type B1).
3. HDL, triglycerides and phospholipids are removed by hydrolysis catalysed by hepatic lipase (HL), endothelial lipase (EL), lipoprotein lipase (LPL) and possibly secretory phospholipase A2.
4. ApoA-I is independently metabolised following its dissociation from HDL during HDL remodelling.
Reference
Barter P, Rye K-A. High density cholesterol: the new target. A handbook for clinicians. Sherborne Gibbs, Birmingham, 2007. CE B TG
VLDL/LDL
Kidney

7. Lipid-poor particles originate from the liver and intestine.
Metabolism of HDL
Lipid-poor particles originate from the liver and intestine.
Plasma apolipoprotein A-I (apoA-I) acquires phospholipids and cholesterol from cell membranes, resulting in discoidal A-I HDL.
Esterification of cholesterol, resulting in formation of spherical HDL.
Remodelling of spherical HDL, leading to changes in composition and size.

8. Cycling of apoA-I between HDLs and a lipid-poor pool
CETP CE TG
Lipid-poor
apoA-I
PLTP
SRB1 HL
HDL
LCAT UC
Discoidal
Excretion through kidney
HDL also transport proteins that are involved in HDL formation and remodelling. These include cholesteryl ester transfer protein (CETP), which remodels HDL into particles of varying size.
Reference
Barter P, Rye K-A. High density cholesterol: the new target. A handbook for clinicians. Sherborne Gibbs, Birmingham, 2007

9. Antiatherogenic Actions of HDL
Anti-infectious activity
Reverse cholesterol transport/cellular cholesterol reflux
Anti-inflammatory activity
Anti-thrombotic activity
Anti-oxidative activity
HDL
In addition to their role in reverse cholesterol transport, HDL have the ability to protect against atherosclerosis via a number of different mechanisms.
HDL have been shown to inhibit oxidative modification of LDL (thereby reducing their atherogenicity) and inhibit expression of endothelial cell adhesion molecules.
HDL also have anti-thrombotic effects, and stimulate nitric oxide generation, thereby reducing endothelial dysfunction. HDL are also implicated in the repair of damaged endothelium.
Reference
Barter P, Rye K-A. High density cholesterol: the new target. A handbook for clinicians. Sherborne Gibbs, Birmingham, 2005
Endothelial repair
Anti-apoptotic acticity
Vasodilatory activity