Lecture 4- 20 Sept 2010
Atherosclerosis
Today
Pathology of atherosclerosis
Introduction to nutritional approaches to atherosclerois
Pathology of atherosclerosis-slide
Atherosclerosis versus arteriosclerosis
Lipids
Platelets
Lipids
-other wise known as fats, oils and waxes
Fatty acids
Saturated
Monounsaturated
Polyunsaturated (w 3 (n-3) and w 6 (n-6))
Cholesterol-free and ester
Triglycerides-fatty acids attached to glycerol backbone
Phospholipids- at least one fatty acid and a polar head group
Lipoproteins-structure and relationship to atherosclerosis
General structure-spherical shape
-cholesteryl ester and triglyceride core
-free cholesterol, phospholipids and apolipoproteins(apoproteins) toward the outside
-this arrangement allows lipids to be carried in water-recall that lipids (cholesteryl ester and triglyceride are poorly soluble in water and that phospholipids and proteins are more soluble in water (why?)
HDL-high density lipoprotein
-HDL cholesterol is known as the good cholesterol
-found in blood serum always
-most of cholesterol is in the form of cholesteryl ester
-high protein to lipid ratio
-apolipoprotein A-I is the major apolipoprotein
-removes cholesterol from artery
LDL-low density lipoprotein
-LDL cholesterol is known as the bad cholesterol
-found in blood serum always
-most of the cholesterol is in the form of cholesteryl ester
-intermediate protein to lipid ratio
-apolipoprotein B-100 is the major apolipoprotein
-deposits cholesterol in arterial wall
VLDL-very low density lipoprotein
-triglyceride is the major lipid
-most of the cholesterol is in the form of cholesteryl ester
-found in blood serum always
-as VLDL blood serum concentration increases the percentage of small dense LDL increases-small dense LDL is very aggressive-what does this mean?
-low protein to lipid ratio
-major lipoproteins are B-100, apo C-II, C-III
Chylomicrons
-found in blood only 8-10 hours post-meal (post-prandial)
-triglyceride is the major lipid
-most of the cholesterol is in the form of cholesteryl ester
-as chylomicron blood serum concentration increases the percentage of small dense LDL increases
- very low protein to lipid ratio
-major apolipoproteins are apo B-48, apo C-II, C-III
Lipoprotein(a)
-similar in structure to LDL
-most of cholesterol is in the form of cholesteryl ester
-apolipoprotein B-100 and apolipoprotein(a) are the
apolipoproteins
-apolipoprotein (a) has a molecular homology with plasminogen- raised platelet aggregation- contrast this with the work of Dr. Barre
-also believed to deposit cholesterol in arterial wall
Metabolism of Lipids
-HDL- apo A-I and the LCAT reaction
-removal of cholesterol from the arterial wall
-LPL reaction and the role of apo C-II and C-III
-inverse relation of LPL activity and HDLc
-VLDL and chylomicrons decrease and HDLc increases
-LDL receptors- and blood serum LDL cholesterol levels
-Fatty acids-omega 3 and 6 paths- relevant to next 2 lectures when we start in on nutrition, nutraceuticals and functional foods relative to atherosclerosis
Response to Injury-injury due to lipid oxidation/blood pressure/infection
-LDL-oxidation-what does it mean
-oxidation induces cell death and reduces endothelial contribution to vasodilation
-Blood pressure-LDL- results in increased blood pressure due to blockage of arterial lumen and as well LDL oxidation resulting in reduced endothelial contribution to vasodilation
-bacterial and viral infection disrupting endothelial cell membrane
Platelets-aggregation slide reminder
-review omega 3 and 6 pathways
-when the platelet is stimulated by collagen
platelet arachidonic acid (AA) produces derivatives that cause aggregation
platelet dihomogammalinolenic acid (DGLA) produces derivatives of DGLA that decrease platelet clumping
platelet eicosapentaenoic acid (EPA) that produces derivatives of EPA that decrease platelet clumping
also platelet DGLA and EPA reduce platelet content of AA-what is the impact of this on platelet aggregation?
-total amount of triglyceride and cholesterol as well as different fatty acids to name but a few
Next lecture- more on diet and atherosclerosis
-functional foods and atherosclerosis
-nutraceuticals and atherosclerosis