Note

Midterm - 7 March in class

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.  

Conversion of 70 mg/dl

To 3.9 mmol/L

Lecture 5a 7 Feb. 2011 Atherosclerosis 

Pathology-5a

Nutritional Intervention-5b

Functional Food/Nutraceutical Approaches-5c

Factors affecting atherosclerosis

Lipids Metabolism review

LCAT, LPL, CETP

Factors affecting atherosclerosisBlood Levels of concern-the more risk factors

(eg obesity and in particular abdominal obesity) the lower the cut off points for

LDL-cHDL-c < 0.90  mmol/L  plasma

                LDL-c  > 3.40 mmol/L plasmaincluding oxidized LDL

                Lp(a) - > 20-30 mg/dl plasma                Cholesterol > 5.20 mmol/L                Triglycerides-fasting > 1.70 mmol/L

plasma                                     -post-prandial

Factors affecting atherosclerosisBlood 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

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

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

Factors affecting atherosclerosis

PlateletsFuster slide

Collagen is the aggregation kick off followed by ADP etc

Platelet membrane fatty acid compositioncyclooxygenase

Platelet membrane fluidity

Factors affecting atherosclerosis

Platelets

Interaction with lipoproteinsHDL-lowers aggregationLDL-elevates aggregation

Lp (a)-depresses platelet aggregation though also thought to inhibit plasminogen activation

Factors affecting atherosclerosis

Blood pressure 

Factors affecting:

Water content of blood-renal functionVasodilationVasoconstriction

Values of concern- > 140 (systolic) or > 90 (diastolic) or >

140/90- significance of these values

Factors affecting atherosclerosis

Obesity-measures

new waist circumference BMISkin foldsUnderwater weighingApple/pear shape

 -elevated blood pressure -triglycerides -elevated LDLc -decreased HDLc

Factors affecting atherosclerosis

Renal Disease

-urea toxic to endothelium (effect)

-cause elevated blood pressure 

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

Factors affecting atherosclerosis

Nitric oxide

-vasodilation, antiplatelet effects

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

Genetics

-Lp (a) – apo (a)

-cholesterol- HMG-CoA reductase

-cyclooxygenase (platelets)

Genetics

-leptin (obesity)

 

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.

Genetics

-immune response

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

Genetics

-nitric oxide synthase

polymorphisms affect level of this enzyme