Transcript 2105Lecture 5a powerpoint

Note
Midterm - 4 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 glucose to 3.9 mmol/L
Lecture 5a 3 Feb. 2014
Atherosclerosis
Pathology-5a
Nutritional Intervention-5b
Functional Food/Nutraceutical Approaches-5c
Atherosclerosis-Pathology
LDL and Lp(a) deposits lipid in artery wall
HDL removes lipid from artery wall
Roles of LCAT, LPL, CETP in these processes
Aggregated platelets also clog up arteries
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 into artery wall
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
-aggregated platelets also clog up the arteries
Factors affecting atherosclerosis
Platelets
Collagen is the aggregation kick off followed by the proaggregatory ADP and TxA2
Aggregation affected by:
Platelet membrane phospholipid fatty acid
composition
-cyclooxygenase produces prostaglandins
-lipoxygenase produces leukotrienes
-review arachidonic acid displacement
Decreased platelet membrane fluidity
-if cholesterol:phospholipid ratio increased
-if degree of membrane fatty acid saturation
increased
-results in increased platelet aggregation
Factors affecting atherosclerosis
Platelets interactions with lipoproteins
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 damage vascular wall causing
increased LDL influx
Factors affecting blood pressure:
-Water content of blood-renal function
-Vasodilation
-Vasoconstriction
Values of concern
- > 140 (systolic) or > 90 (diastolic) or >
140/90
Factors affecting atherosclerosis
Obesity
-measures
waist circumference
waist to hip and waist to height
BMI
skin folds
underwater weighing
apple/pear shape
-obesity causes the following:
-elevated blood pressure and renal disease
-elevated plasma triglycerides
-elevated plasma LDLc and sd LDLc
-decreased plasma HDLc
Factors affecting atherosclerosis
Renal Disease
-urea builds up in blood and is toxic to
endothelium (results in reduced vasodilation)
-renal disease causes further elevated blood
pressure due to reduced water clearance
from the blood and reduced
vasodilation
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-increased levels give
vasodilation, antiplatelet effects
Factors affecting atherosclerosis
Genetics
-HDL- LCAT, CETP
-LDL- LDL receptor
-VLDL- LPL (apo C-II-activation, C-III)
inhibition)
-
-chylomicrons-LPL
Genetics
-Lp (a) – apo (a)
-cholesterol- HMG-CoA reductase
-platelets-cyclooxygenase and lipoxygenase
Genetics
-leptin (obesity)
Genetics
-immune response
adequacy of response in part governed
genetically-possible implications include the
infection/inflammatory issues mentioned above
Genetics
-nitric oxide synthase
-nitric oxide synthase gene polymorphisms
affect level of this enzyme and hence nitric
oxide levels