Atherosclerosis and peripheral vasc disease Flashcards
Modifiable risk factors of atherosclerosis?
smoking lipid intake BP diabetes obesity sedentary lifestyle
What are non-modifiable risk factors atheroscleorsis?
Age
Sex
Genetic background
ABCD? Do decide which med to give
Ace inhibitors
Beta blockers
C
Diuretics
What can be given for obestiy?
Weight loss gastric surgert metformin insulun dietry advice
What has reduced hyperlipidaemia over the last decade?
statin treatment
What has reduced hypertension over the last decade?
antihypertensive treatment
What has increased diabetes in the last decade?
Increased obesity
- New improvements in diabetes treatment have doubtful effect on macrovascular disease
Which vessels are affected most by atheroscleorisis?
Coronary
Cerebral
Carotid
Iliac
tend to occur in bifurcations, branches, bends due to turbulent blood flow. This can cause inflammation
What is LDL deposition?
Atherescleorsis happens in between the internal elasric and intima usding LDL dposition
How doe LDL bind?
depost in subintimal space and binds to matrix proteoglycans
Describe the progression of atherosclerosis?
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When is the window of opportunity for primary prevention?
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When is clinical intervention eeded?
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What is the role of vascular smooth. muscle cells?
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What are vascular endothelial cell for?
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What are Platelets for?
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What are T lymphocytes for?
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What did the cantos trial show?
Inflammation involved in atherosclerosis:
px at high risk injected with antibodies to IL-1
lead to fewer major adverse cardiovascular events - MACE
Multiple mechanisms including cholesterol crystal formation connect lipids and inflammation in atherosclerosis
what did zohaa say to jiya on 3/12/21 10:29?
im gonna be so lonely stuck in reynolds u better or i will replace u with the better rashid
what did zohaa say to jiya on 3/12/21 10:29?
im gonna be so lonely stuck in reynolds u better or i will replace u with the better rashid
macro
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WHat two classes of macrophages are therw?
inflammatory
resident
How are macrophage subtypes regulated?
combinations of transcription factors binding to regulatory sequences
Why is white blood cell regulation vital?
cells can injure host tissue if they are activated excessively or inappropriately!
WHich are the main inflammatory cells in atherosclerosis?
macrophages
What do inflmmatory macrophages do?
Adapted to kill microorganisms (germs)
Which resident macrophages are thee?
normal homeostatic - suppress inflammatory activity
alveolar resident macrophages - surfactant lipid homeostasis
osteoclasts - keep Ca + Phosphate under tight regulation
spleen - takes abnormal, old RBCs out of the blood
Which resident macrophages are thee?
normal homeostatic - suppress inflammatory activity
alveolar resident macrophages - surfactant lipid homeostasis
osteoclasts - keep Ca + Phosphate under tight regulation
spleen - takes abnormal, old RBCs out of the blood *old rbc get stiff and stuck in narrow vessels of spleen == iron homeostasis
What are LDLS, where are they made and taken?
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What are HDLs, what does it do?
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What are oxidised LDLs, modified LDLs?
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describe the structure of an LDL?
Centre : cargo fat for fuel, TG and CE
surrounded by lipid monolayer
cholesterol in membrane
apoprotein on top
How are oxidised LDLs made?
LDLs leak through th endothelial barrier
LDL binds to maxtric proteoglycans in subendothelial layer = becomes susceptible to modification
LDL becomes oxidatively modifited by free radicals
How do macrophages cause chronic inflammation via LDLs?
Oxidised LDLs are phagocytosed by macrophages and stimulates chornic inflammatipn
WHat are foam cells?
When macrophage has take up LDLs
What is familial hyperlipidemia?
- Autosomal genetic disease
- Massively elevated cholesterol (>~20 mmol/L). (effective ‘normal’ ~1-5 mmol/L)
Failure to clear LDL from blood.
= Xanthomas and early atherosclerosis;
if untreated fatal MYOCARDIAL INFARCTION before age 20.
slide 24?
24
macrophage receptor A?
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/macrophage receptor B\?
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WHich enzymes do macrophages have?
ocidative:
NADPH oxidase
Myeloperoxidase e.g.HOCl …
How are monocytes recruited?
Plaque macrophages express inflammatory factors that are involved in monocyte recruitment.
Which cytokines are involved with self perpetuating inflammation?
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Which chemokines are involved with self perpetuating inflammation
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What do VSMC do?
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How are VSMC recruited?
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What is platelet dderived growth factor used for?
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WHat does the transforming grwoth factor beta?
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How do normal medial vascularr smooth muscles become atherosclerotic?
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What are metalloproteinases? (expressed by mcarophaes)
Family of ~28 homologous enzymes.
Activate each other by proteolysis.
Degrade collagen.
Catalytic mechanism based on Zn.
What are the effects of plaque erosion?.
Blood coagulation at the site of rupture may lead to an occlusive thrombus and cessation of blood flow.
What are the chatacteristics of a vulnerable plaque which can become ruptured?
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describe macrophage apoptosis?
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What is the nuclear factor Kappa B?
TF
How does NFkB coregulate different inflammatory genes?
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