Note

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Note Midterm - 7 March in class
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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.  
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Conversion of 70 mg/dl To 3.9 mmol/L
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Lecture 5a 7 Feb. 2011   Atherosclerosis   Patho
logy-5a Nutritional Intervention-5b Functional
Food/Nutraceutical Approaches-5c
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Factors affecting atherosclerosis
Lipids Metabolism review LCAT, LPL, CETP
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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 lt 0.90 
mmol/L  plasma                 LDL-c  gt 3.40
mmol/L plasma including oxidized
LDL                 Lp(a) - gt 20-30 mg/dl
plasma                 Cholesterol gt 5.20
mmol/L                 Triglycerides-fasting gt
1.70 mmol/L plasma                        
             -post-prandial
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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     CholesterolHDL-c ratio High    
gt 20        lt 2.0
mmol/L                    lt 4.0
Moderate           11-19         lt
3.5 mmol/L                    lt
5.0 Low                               lt 10 
       lt   5.0 mmol/L                  lt
6.0   or history of diabetes or any
atherosclerotic disease - Can. J. Cardiol 22
913-end                      September 2006
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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
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Factors affecting atherosclerosis Macrophages Ox
idation 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
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Factors affecting atherosclerosis Platelets Fust
er slide Collagen is the aggregation kick off
followed by ADP etc Platelet membrane fatty
acid composition cyclooxygenase Platelet
membrane fluidity
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(No Transcript)
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Factors affecting atherosclerosis Platelets Inte
raction with lipoproteins HDL-lowers
aggregation LDL-elevates aggregation Lp
(a)-depresses platelet aggregation though also
thought to inhibit plasminogen activation
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Factors affecting atherosclerosis Blood
pressure   Factors affecting Water content
of blood-renal function Vasodilation Vasoconst
riction Values of concern - gt 140 (systolic)
or gt 90 (diastolic) or gt 140/90 -
significance of these values
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Factors affecting atherosclerosis Obesity -measu
res new waist circumference
BMI Skin folds Underwater
weighing Apple/pear shape   -elevated blood
pressure -triglycerides -elevated LDLc
-decreased HDLc
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Factors affecting atherosclerosis Renal
Disease -urea toxic to endothelium
(effect) -cause elevated blood pressure  
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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
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Factors affecting atherosclerosis Nitric
oxide -vasodilation, antiplatelet effects
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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
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Genetics -Lp (a) apo (a) -cholesterol-
HMG-CoA reductase -cyclooxygenase
(platelets)
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Genetics -leptin (obesity)  
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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.
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Genetics -immune response adequacy of
response in part governed genetically-possible
implications include the infection/inflammatory
issues mentioned above
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Genetics -nitric oxide synthase polymorphism
s affect level of this enzyme