Therapeutics of Cardiovascular Diseases Lipid-Lowering Drugs and Atherosclerosis 2008 George Hsiao Institute of Pharmacology, TMU
Structure of Lipoprotein Particles
Lipoproteins provide a means of transporting lipids (cholesterol, triglycerides, and phospholipids), which are insoluble in the blood, around the body.
Four classes of lipoproteins exist. These differ in size, density, constituent lipid, and type of surface protein (apoprotein). They are:
High-density lipoproteins (HDL)
Low-density lipoproteins (LDL)
Very-low-density lipoproteins (VLDL)
Lipid transport in the blood is via two pathways
In the exogenous pathway:
1. Diet-derived lipid breakdown leads to the formation of chylomicrons.
2. Lipoprotein lipase (LPL), found in the endothelium of extrahepatic tissues, hydrolyses the triglycerides in chylomicrons to glycerol and fatty acids (FFAs), for use by the tissues.
3. The chylomicron remnant is taken up by the liver.
4. The liver secretes cholesterol and bile acids into the gut, creating an enterohepatic circulation.
In the endogenous pathway:
1. The liver secrets VLDLs, the components of which may be derived either endogenously or from the diet.
2. Lipoprotein lipase (LPL), found in the endothelium of extrahepatic tissues, hydrolyses the triglycerides in chylomicrons to glycerol and fatty acids (FFAs), for use by the tissues, and leaves LDL.
3. LDL is then taken up by the liver and extrahepatic tissues.
4. HDL is secreted by the liver into the plasma, where it is modified by lecithin cholesterol acyltransferase (LCAT) and taken of cholesterol from the tissues. Lecithin cholesterol acyltransferase (LCAT) transfers cholesterol esters to LDLs and VLDLs.
Hyperlipidaemias are characterized by markedly elevated plasma triglycerides, cholesterol, and lipoprotein concentrations.
Cholesterol is deposited in various tissues. Deposition in arterial plaques results in atherosclerosis, which leads to heart attacks, strokes, and peripheral vascular disease. Deposition in tendons and skin results in xanthomas.
Primary hyperlipidaemias are genetic, and numerous types exist.
Secondary hyperlipidaemias are the consequences of other conditions such as: