Transcript this is due to low LPL activity Factors affecting atherosclerosis

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 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
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
LDL-c level
Cholesterol:HDL-c ratio
> 20 %**
< 2.0 mmol/L
< 4.0
Moderate
11-19 %
< 3.5 mmol/L
< 5.0
Low
< 10 %
< 5.0 mmol/L
< 6.0
High
Risk
** 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
Platelets
Fuster slide
Collagen is the aggregation kick off followed
by ADP etc
Platelet membrane fatty acid composition
cyclooxygenase
Platelet membrane fluidity
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
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
Factors affecting atherosclerosis
Obesity
-measures
new waist circumference
BMI
Skin folds
Underwater weighing
Apple/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-IIactivation, 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