Atherosclerosis and lipid metabolism Flashcards
What are some untreatable and potentially treatable risk factors for CVD?
Untreatable
- Gender –> men > women
- Age –> >45 men, post-menopause women
- Genetic traits
- Psychosocial
- Low socio-economic
- Stressful situations
- Coronary prone behaviour patterns –> Type A behaviour
Potentially treatable
- Smoking and sedentary behaviours
- Dyslipidaemia –> increased cholesterol, TAG, LDL and VLDL lipoprotein levels, decreased HDL
Oxidability ofLDL
Hypertension
Hyperglycaemia, T2D and metabolic syndrome
Pro-thrombic factors –> elevated ability to not break down clots, thrombus formation. Those at risk of CVD might have elevated levels of Plasminogen activator inhibitor which inhibits the breakdown of blood clots, which is dangerous if suffering from atherosclerosis.
High homocysteine levels (produced by liver –> Can inhibit nitric oxide, responsible for vasodilation. Also related to hyperinsulinaemia. Can increase sodium retention which is linked to hypertension
What risk factors for CVD may diet modulate?
Dyslipidaemia
- Increased cholesterol, TAG, LDL and VLDL
- Decreased HDL
Oxidability of LDL
Pro-thrombic factors (PAI-1)
High homocysteine levels (oxidative stress)
Hypertension (Angiotensin –> activates plasminogen activator inhibitor 1
Central obesity, hyperglycaemia, T2D and metabolic syndrome
Why is cholesterol important in diet?
- Hormone production –> precursor to bile acid
- Cell membrane fluidity
Not necessarily needed through diet, however it can be made in the body. If high level are brought in through diet, then the body won’t make as much.
Why should LDL not be between smooth muscle and endothelium?
It can cause damage to the endothelial layer which allows LDL to migrate into that area. Macrophages will engulf LDL and form foam cells. These cells can only expand to a certain point before they become necrotic (producing death of a usually localised area of living tissue) causing the contents to spill out and form the atherosclerotic plaque
What are different types of dietary fat?
- Saturated fatty acids –> storage, quick energy source
- MCFAs
- MUFAs
- PUFAs
- Long chain polyunsaturated fatty acids
- n-3, n-6, n-9 unsaturated fatty acids
- Cis/ trans fatty acids –> rigid structure –> banned in Denmark where a decrease in CVD has been seen
- Cholesterol
What is the danger of having high levels if visceral obesity?
- Altered FFA metabolism
- Altered adipokine release
- Increased liver fat and altered function
- Increased epicardial fat
- Increased muscle fat –> increase in intracellular lipids
- Altered metabolic profile
- Increase risk of stroke, heart disease, T2D
- ‘Active fat’
- Associated with insulin resistance which can lead to glucose intolerance and type 2 diabetes. Visceral fat secretes a protein called retinol-binding protein 4 (RBP4) which has been shown to increase insulin resistance
- Increase in TNFa and Il6
- FFA enter portal veins to the liver where it can influence the production of blood lipids and lead to NAFLD
What fats are the highest in unsaturated fat and saturated fat?
Saturated
- Coconut oil
- Cocoa butter
- Butter
- Lard
Monounsaturated
- Sunflower oil
- Olive oil
- Canola oil
- Peanut oil
How are lipid absorbed?
Food enter intestine from stomach
- Emulsification of fat droplets by bile salts (Bile salts are synthesised by cholesterol)
- Hydrolysis of triglycerides in emulsified fat droplets into free fatty acid and monoglycerides by using pancreatic lipase
- Free fatty acids and monoglycerides are packed into micelles which are coated in bile acids, has a hydrophobic and hydrophilic part.
- Micelles can interact with transporters or diffuse across enterocyte membrane and be reconstituted into triglycerides.
- Taken up by enterocytes
- Triglycerides combine with enzymes and are packaged up in chylomicrons
- Chylomicrons deliver absorbed TAG to cells
Another version
Dietary TAG are emulsified by bile acids (which are synthesised by cholesterol)
Emulsified TAG are hydrolysed into FFA and monglycerides which with pancreatic lipase get packaged into micelles.
Micelles allow absorption of FFA and monoglycerides into the enterocyte/ mucosal cell, which then reassemble as TAG
Triglycerides combine with enzymes and are packaged up into Chylomicrons
Chylomicrons leave the mucosal cells and are released via the lymphatic system, not deposited directly into blood due to large size
Chylomicrons deposited into blood from licelles and acted on by lipoprotein lipase where TAG are cleaved off and enters cell
The removal of triglycerides results in the formation of chylomicron remnants which then binds liver remnant receptor which then causes it to be repackaged and modified to produce VLDL.
What are micelles
What free fatty acids and monoglycerides are packaged into by pancreatic lipase following hydrolysis of emulsified fat droplet.
Coated in bile acids
Once lipids leave, the bile acid conjugates can be taken back to the liver to be recycled and any unabsorbed material exits via faeces
How are lipids secreted from enterocytes?
- Inside enterocyte MAG and FFA re-synthesised into TAG
- TAG packaged with cholesterol and fat soluble vitamins into chylomicrons
- Chylomicrons are lipoproteins –> transport lipids in circulation
- Chylomicrons released by exocytosis from enterocytes
- Too large to enter capillaries so enter lacteals which are lymphatic capillaries that poke up into the centre of each villus.
- Form chyle –> lymph fluid and emulsified fats
- Lacteals to form larger lymphatic vessel
- Chyle transported to the thoracic ducts where it is then emptied into the bloodstream
- Chylomicrons transports TAG where are used in places such as skeletal muscle, cardiac muscle, adipocytes, hepatocytes
What is the generic structure of low density lipoprotein?
LDL
- Hydrophilic surface of phospholipids and free cholesterol
- Hydrophobic core of triacylglycerols, cholesterol esters and lipid soluble vitamins
- Integral apoprotein e.g. apoB100 –> good way of detecting LDL and VLDL in circulation –> crosses into core
- Peripheral apoprotein (on outside) e.g. apoE –> a protein that reacts with an apoE receptor at the liver so it can be internalised and discharge any excess into the liver –> allow cell interaction
LDL, HDL, IDL and VLDL interact with each other and are dependent on each other for their function
Share peripheral apoproteins to allow cell interaction for discharge or take up of contents
Components (hydrophilic coat)
- Phospholipids
- Protein
- Free cholesterol
Cargo (hydrophobic)
- TAG
- Cholesterol esters –> for H bonds with water
Describe chylomicron structure
Very large
Contain TAG –> most of lipid
Little protein –> ApopC 1, 2 and 3 –> can be added in circulation if needed
What is VLDL?
Very low density lipoprotein
- Made by liver to transport lipids to various tissues in the body
- Majority of lipid is triglyceride
- 8% protein –> ApopB100, C 1, 2, ApoE
What is IDL?
Results from catabolism of VLDL
Leftover part after triglyceride removed
Converted to LDL by liver
Major lipid is cholesterol esters –> when in arterial space, as macrophages engulf to form foam cells, esters taken with it which forms plaque.
Proteins 15% –> ApoB100, ApoC, ApoE
What is LDL
Major lipid is cholesterol
Delivers cholesterol from liver to cells
- Cell membranes
- Hormone production
Protein 21% –> ApoB100
Binds to LDL specific receptor
