atherosclerosis Flashcards
how has the prevalence of ischaemic heart disease changed?
has moved from number 5 to number 1
why has the prevalence increased?
- diet has changed
- global increase in obesity, diabetes, hyperlipidemia and hypertension
what are modifiable risk factors?
- smoking
- lipid intake
- blood pressure
- diabetes
- obesity
- sedentary lifestyle
what are non modifiable factors?
- age
- sex
- genetic background
what have been the changes in epidemiology over the last decade?
- reduced hyperlipidemia
- reduced hypertension
- increased obesity
- more diabetes
- ## improvements in diabetes treatment
where do the fat deposits sit?
- plaque happens at places with ordered blood flow
***what part of the artery does the fat bind to?
the fat binds to the intima
the LDL deposit in the subintimal space and binds to the matrix proteoglycans
*****how does atherosclerosis progress in terms of lesions?
- as people get older the plaque grows in small steps rather than smoothly
- when the plaque starts to break up it is dangerous
what are the main cell types involved in atherosclerosis?
- vascular endothelial cells
- monocyte macrophages
- vascular smooth muscle cells
- platelets
- T lymphocytes
function of vasuclar endothelial cells?
- barrier function
- leukocyte recruitment
function of monocyte macrophages?
monocytes turn into macrophages
- needed for foam cell formation
- cytokine and growth factor release
- major source of free radicals
- metalloproteinases
function of vascular smooth muscle cells?
- migration and proliferation
- collagen synthesis
- remodelling and fibrous cap formation
function of platelets?
thrombus generation
- Cytokine and growth factor release
function of T lymphocytes?
Macrophage activation
what do macrophages do?
they are white blood cells derived from monocytes that if activated excessively can damage host tissue
what are the macrophage subtypes ?
what do they do ?
- inflammatory macrophages
- adapted to kill microorganisms
- resident macrophages
- normally homeostatic so suppress inflammatory activity
- osteoclasts - calcium and phosphate homeostasis
- spleen - iron homeostasis
what is LDL ( low density lipoproteins)
- bad cholesterol
- synthesised in the liver
- carries cholesterol from shelver to the rest of the body
what s HDL? ( high density )
- good cholesterol
- carries cholesterol from the peripheral tissues and arteries back to the liver
what are oxidised LDLs?
due to the action of free radicals on LDL
-
***what is the structure of LDL?
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how does the LDL become modified?
- LDLs leak through the endothelial barrier by uncertain mechanisms
- the LDL is stuck by binding to the proteoglycans in the sub endothelial layer and become susceptible to modification
- modification is normally oxidation
- the LDL becomes oxidised by the free radicals and the oxidised LDL is phagocytesed by macrophages and causes inflammation
***what is the overall mechanism of LDL -> chronic inflammation?
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what is familial hyperlipidemia?
- it is an autosomal genetic disease
- which is basically massively elevated cholesterol
- it is when the LDL cannot be cleaned form the blood
- fatal
what types of LDL receptors are there?
there are two types
what happens if there is no LDLR?
- the macrophages accumulate cholesterol
what does the second LDL receptors do?
what are they called
- they are called scavenger receptors since they hoover up chemically modified LDL
- they accidentally bind to Oxidised LDL
what are statins?
HMG coA reductase inhibitors
reduce plasma cholesterol
what are the types of macrophage scavenger receptors?
macrophage scavenger receptor A
- Known as CD204
- Binds to oxidised LDL
- Binds to Gram-positive bacteria like Staphylococci & Streptococci
- Binds to dead cells
macrophage scavenger receptors B
- Known as CD36
- Binds to oxidised LDL
- Binds to malaria parasites
- Binds to dead cells
what do macrophages do to LDL
using what enzymes?
step 1
macrophages modify the LDL
using. ..
- NADPH oxidase
- Myeloperoxidase
what do macrophages do to the modified LDLs?
step 2
they accumulate the modified LDLs to become enlarged foam cells
what do the plaque macrophages express?
inflammatory factors that are involved in monocyte recruitment
