Lecture 28: Inflammation and Coronary Artery Disease Flashcards
What pathologies do atherosclerosis underly?
Coronary, cerebra, and peripheral vascular diseases
What constitutional risk factors for atherosclerosis?
Genetics
Family History
Age
Male
What modifiable risk factors for atherosclerosis?
Hypertension and Hyperlipidemia Smoking Diabetes Vitamin Deficiencies Obesity Sedentary lifestyle Inflammation
What are some inflammatory markers?
High sensitivity C-reactive protein (HSCRP)
Acute phase interleukins: IL-1, IL-6
Serum amyloid A
What are some pro-coagulant markers?
Plasma homocysteine
Tissue plasminogen activator
Plasminogen activator inhibitor
Lipoprotein A
Where do most lesions happen in vasculature?
Where turbulence is more likely to happen
- openings of exiting vessels
- branch points
- posterior abdominal aorta
What interleukins promote expression of P and E selectins on the endothelium?
IL-1
TNF
What type of leukocyte does IL-8 attract?
Neutrophils
What receptor on macrophages take up oxidized lipids?
CD 36
TLR-4
What factors are important for smooth muscle cell proliferation?
PDGF
Fibroblast growth factor
TGF-α
What adaptive immunity cells play a role in smooth muscle proliferation?
Th1
Th17
B cells
How are fatty streaks formed?
Expansion from foam cells and extracellular lipid
- recruited inflammatory and smooth muscles cells
- increased ECM
How do atherosclerotic plaques form?
Fatty streak is covered with fibrous cap
- center is nectroic
- surrounded by zone of inflammatory and smooth muscles cells
What causes plaque instability
Fibrous cap is degraded but not resynthesized
-physical stresses can cause plaque to rupture
In new studies, what interleukin is being targeted in treating atherosclerosis?
IL-1β (CANTOS study)
-Unfortunately, canakinumab was not approved due to no significant reduction of inflammation
