28. Inflammation & CAD Flashcards
what are the non-modifiable risk factors for athersclerosis
genetic abnormalities
FHx
age
male
what are the modifiable risk factors for athresclerosis
lifestyle changes
inflam
hyperlipidemia, HTN, DM
vit B6 deficiency
what are the procoagulant markers
plasma homocysteine
tPA
plasminogen activator inhibitor
lipoprotein A
what are the inflam markers that increase risk for athresclerosis
HSCRP
acute phase ILs (IL-1, IL-6, TNF)
serum amyloid A
possible chronic infection
prgenancy associated plasma protein A
where do most athresclerosis lesions occur
at openings of exiting vessels
branching poinds
post abd aorta
-bc increased risk of hemodynamic turbulence
rate the vessels impacted by athresclerosis in severity
worst - abd aorta
coronary As
popliteal As
ICA
least severe- circle of willis
what is an activated endothelial state & when does it happen
endothelial tissue injury ==> become procoagulant with the following phenotypes:
pro inflam
prothromnogenic
–> lead to initiation of thromobus formation, athresclerosis & vascular lesions in HTN
what increases the expression of P & E selectin on the endothelium
IL-1 & TNF (secreted by macrophages)
-slow leukocytes down & responde to chemokines (IL-8)
what is the role of circulating macrophages in arthersclerosis
cholesterol & cholesterol esters (lipids) form plaque in intima
–> macrophages take up the oxLDL –> accumulate and turn into foam cells –> create fatty streaks –> stimulate inflam response
what causes the recruitment of leukocytes in endothelial damage
tissue macrophases release IL-1, IL-6, IL-8 & TNF
which complement pathway is active in inflammation
alternative pathway
C3BbP –> C5a & C3a - recruit more neturophils & monocytes
what is the fxn of the kinin cascade during inflam
vasodilation, increase permeability of blood vessels and stimulate pain receptors
which receptor is specific for oxLDL on macrophages &
what happens onces they bind?
scavenger receptor CD36 (lipid can also bind TLR-4)
activate/differntiate M1 tissue macrophages –> proinflam response
what does the activation & differentiation to M1 tissue macrophages cuase in inflam
production & relase of acute phase cytokines
transformation to foam cells
cholesterol crystals with foam cells –> promote inflammasome activity
what is the result of activating the NLRP3 inflammasome from the cholesterol crystals?
produce and secrete IL-1beta & IL-18
what do cholesterol crystals & IL-1 induce in neutrophils
release of NETs and DAMPs
nets = prothombogenic
-lay down scaffold for platelet/RBC activation, aggregation & thrombosis
what are the effects of elastase released by neutrophils
decreased elascticity in vessels
which adaptive immune cells are most involved in arthresclerosis
Th1
Th17
B-cells
why do T & B cells react to our own cells during atherosclerosis
oxLDL isnt the same molecule thats present during development
what causes the atherosclerotic plaque
soft fatty streaks become covered w/ fibrous caps
center is necrotic w/ lipids, debris, foam cells & thrombus
surrounded by zone of inflammatory & Sm. M
what is the most significant inflam marker for CV risk
HSCRP
what levels of HSCRP is considered high risk for CV disease
> 3 mg/L
what was the outcome of the anti-inflam canakinumab trial
not significant enough decrease in risk for CV disease
what happens when endothelium is injured and taken out of its basal state
-upregulation of procoagulants,
adhesion molecules & proinflam factors
- altered expression of chemokine, cytokines & growth factores
what happens after activation of adaptive immunity
increased
- adhesion molecule expression
- release of cytokines/chemokines
- increase MHC/HLA II expression
- increased oxLDL uptake
- increase macrophage activaiton
ACC-MHOM
what happens if you have a a thick fibrous cap
thrombosis erosion
how can a fibrous cap become thin/weak
increase inflam –> accelerate fibrous cap degradation & inhibit resynthesis –> decrease collagen –> weaken
what can happen if a fibrous cap is thin
rupture
