1. Note Midterm - 7 March in class

2. Note Signal peptide-A sequence of amino acids that determine whether a protein will be formed on the rough endoplasmic reticulum or on free ribosomes. Note: all protein synthesis begins on free ribosomes.sequenceamino acidsprotein rough endoplasmic reticulumribosomes

3. Conversion of 70 mg/dl To 3.9 mmol/L

4. Lecture 5a 7 Feb. 2011 Atherosclerosis Pathology-5a Nutritional Intervention-5b Functional Food/Nutraceutical Approaches-5c

5. Factors affecting atherosclerosis Lipids Metabolism review LCAT, LPL, CETP

6. Factors affecting atherosclerosis Blood Levels of concern-the more risk factors (eg obesity and in particular abdominal obesity) the lower the cut off points for LDL-c HDL-c < 0.90 mmol/L plasma LDL-c > 3.40 mmol/L plasma including oxidized LDL Lp(a) - > 20-30 mg/dl plasma Cholesterol > 5.20 mmol/L Triglycerides-fasting > 1.70 mmol/L plasma -post-prandial

7. Factors affecting atherosclerosis Blood Levels of concern-the more risk factors (eg obesity and in particular abdominal obesity) the lower the cut off points for LDL-c Risk Category Risk LDL-c level Cholesterol:HDL-c ratio High > 20 %** < 2.0 mmol/L < 4.0 Moderate 11-19 % < 3.5 mmol/L < 5.0 Low < 10 % < 5.0 mmol/L < 6.0 ** or history of diabetes or any atherosclerotic disease - Can. J. Cardiol 22: 913-end September 2006

8. Factors affecting atherosclerosis Triglycerides and small dense LDL As plasma triglyceride levels rise there is a greater percentage of small dense LDL -small dense LDL is taken up very aggressively Triglycerides and low HDL -this is due to low LPL activity

9. Factors affecting atherosclerosis Macrophages Oxidation of LDL results in the binding of monocytes to the endothelial cells lining the vessel wall. These monocytes are activated and migrate into the endothelial space where they are transformed into macrophages, leading to further oxidation of the LDL. The oxidized LDL is taken up through the scavenger receptor on the macrophage, leading to the formation of foam cells

10. Factors affecting atherosclerosis Platelets Fuster slide Collagen is the aggregation kick off followed by ADP etc Platelet membrane fatty acid composition cyclooxygenase Platelet membrane fluidity

12. Factors affecting atherosclerosis Platelets Interaction with lipoproteins HDL-lowers aggregation LDL-elevates aggregation Lp (a)-depresses platelet aggregation though also thought to inhibit plasminogen activation

13. Factors affecting atherosclerosis Blood pressure Factors affecting: Water content of blood-renal function Vasodilation Vasoconstriction Values of concern - > 140 (systolic) or > 90 (diastolic) or > 140/90 - significance of these values

14. Factors affecting atherosclerosis Obesity -measures new waist circumference BMI Skin folds Underwater weighing Apple/pear shape -elevated blood pressure -triglycerides -elevated LDLc -decreased HDLc

15. Factors affecting atherosclerosis Renal Disease -urea toxic to endothelium (effect) -cause elevated blood pressure

16. Factors affecting atherosclerosis Various Pathogens -chlamydia pneumoniae -cytomegalovirus -heliobacter pylori -these agents are hypothesised to inflame the endothelium thus permitting influx of LDL -the exact role if any of pathogens in atherosclerosis is yet to be worked on

17. Factors affecting atherosclerosis Nitric oxide -vasodilation, antiplatelet effects

18. Factors affecting atherosclerosis Genetics -HDL- apo A-I, LCAT, CETP -LDL- apo B-100, LDL receptor, scavenger receptor -VLDL -apo B-100, LPL (apo C-II- activation, C-III inhibition) -chylomicrons- apo B48, LPL

19. Genetics -Lp (a) – apo (a) -cholesterol- HMG-CoA reductase -cyclooxygenase (platelets)

20. Genetics -leptin (obesity)

21. Genetics -angiotensin converting enzyme (kidney) The major regulator of mineralocorticoid synthesis is the renin/angiotensin system. Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II, a potent vasoconstrictor and stimulator of aldosterone secretion by the adrenal gland. High circulating plasma ACE is associated with high circulating levels of PAI-1 (plasminogen activator inhibitor-1), the major inhibitor of fibrinolysis in the circulation.

22. Genetics -immune response adequacy of response in part governed genetically-possible implications include the infection/inflammatory issues mentioned above

23. Genetics -nitric oxide synthase polymorphisms affect level of this enzyme