Unit 2 Day 5 (Mon 4/13) Flashcards
1
Q
CVD Prevalence
A
- inc. with age
- initially most common in men, but as age inc. it becomes more common in women
2
Q
Steps in Atherosclerotic Process
A
- LDL infiltrates into sub endothelial space
- LDL is oxidized
- release of inflammatory cytokines and inc. expression of adhesion molecules
- monocytes recruited to clean up oxidized LDL
- phagocytosis of LDL leads to foam cell formation
- foam cells and T lymphocytes within plaque secrete MMP
- secretion and activation of tissue factors
- plaque rupture occurs in unstable lesions, leading to vessel thrombosis and acute coronary events
3
Q
Lipid Metabolism- Exogenous
A
- dietary
- processed into chylomicrons (E, C2, B48)
- LPL removes triglycerides from chylomicrons = remnant
- remnant binds to remnant receptor on liver
- taken up by liver and cleared from body
4
Q
Lipid Metabolism- Endogenous
A
- VLDL particles made by liver (proteins E, C2, B100)
- LPL removes triglycerids from VLDL to form smaller IDL
- IDL exposed to more LPL eventually forms LDL with only B100 protein
- LDL binds LDL receptor on liver
5
Q
Statins
A
-upregulate LDL receptor on liver to dec. LDL in bloodstream
6
Q
HDL
A
- removes cholesterol and replace with triglycerides
- CTP protein lowers HDL levels
- tries to remove cholesterol from body
- HDL is good
- under chronic inflammatory state, HDL may be no longer effective
7
Q
Current Guidelines for Treating Blood Cholesterol
A
- 4 major statin benefit groups
- individuals with known clinical ASCVD
- individuals with LDL >190 mg/dl
- individuals with diabetes (>40 yo and LDL >70)
- individuals (>40, LDL>70) w/o ASCVD or diabetes who have est. 10 yr ASCVD risk >7.5%
8
Q
Hypertiglyceridemia
A
- associated with acute pancreatitis
- unclear whether lowering TG is beneficial
9
Q
Why is inflammation implicated in atherogenesis?
A
- evolution of host response to bacterial infection inc. risk of sterile inflammation
- PAMPs
- DAMPs (oxidized LDL, cholesterol crystals)
- innate immune cell interaction with endothelium drives initial plaque formation
10
Q
Monocyte Adhesion
A
- VCAM1 on endothelium binds to CD11c and VLA4 on monocyte (oxidized LDL promotes expression of VCAM)
- adhesion is obligate step in atherosclerosis
- knocking out VLA-4 and CD 11c inhibits monocyte adhesion and limits atherosclerosis
11
Q
Adaptive Immunity in Atherogenesis
A
- dendritic cell presentation and subsequent T cell activation promotes T cell expansion
- Th1 response promotes IFNg elaboration and atherosclerosis
- Th17 may promote plaque instability
- T cells promote lesions expansion and plaque vulnerability
12
Q
Major Drivers of Plaque Instability
A
- Macrophage apoptosis and necrosis promotes a “necrotic core”
- Matrix metalloproteinases degrade the fibrous cap (secreted by macrophages)
- Intra-plaque hemorrhage further weakens core
13
Q
C Reactive Protein
A
- possibly expressed by macrophages and smooth muscle cells
- activates classical complement pathway
- high CRP-high LDL combined leads to dec. probability of event-free survival
- predicts excess risk of CV events after accounting for standard risk factors
14
Q
Role of Inflammation and Atherosclerosis
A
- impaired HDL efflux capacity associated with more psoriasis
- also related to RA
- inc. monocyte/macrophage activation: common mechanism underlying many autoimmune diseases
- tx of autoimmune disease may be associated with lower risk of CV events
15
Q
Prevalence of Peripheral Vascular Disease and Risk Factors
A
- adult prevalence = 10-20%
- risk factors: diabetes, smoking, lipids, hypertension
- PAD has 6x inc. risk of CV death
