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Flashcards in Atherosclerosis Deck (46):
1

What are 3 endothelial cell adhesion mcs?

VCAM 1
ICAM 1
E-selectin

2

What is a foam cell?

Macrophage rich in cholesterol and cholesterol esters

3

Which kinds of T cells play a role?

Inflammatory TH1 lymphocytes play a role in lesion initiation, progression and instabilty-plaque rupture. Express IL-12, INF-gamma and TNF alpha which perpetuates macrophage and T cell proliferation.

*Also inc MMPs that degrade matrix and cap, while reducing sm cell proliferation and formation of the cap

4

What is obligatory for lesion initiation and prog?

Macrophages and LDL

5

Are lymphocytes obligatory for lesion initiation and prog?

No, but they exert a net pro atherogenic effect under less atherogenic pressures

6

What is HDL's role in atherosclerosis?

-Antiinflammatory effects (dec in adhesion mcs)
-HDL enters sub-endo space and effluxes cholesterol from macrophages/foam cells and then returns to plasma and carries that cholesterol to the liver for excretion
-inhibits LDL ox
-Upregulates prostacyclin and NO in endothelium and suppresses thrombosis

7

What signals for the change in sm phenotype?

Intigrins, adhesion mcs and chemokines produced in early lesions signal to medial smooth muscle cells

8

What changes in phenotype do sm's have?

-Switch from contractile to synthetic
-Migrate into neointima
-Undergo limited proliferation
-Secrete lareg amt of matrix
-Secrete cytokines, chemokines, growth factors and inflammatory prostaglandins
-Migrate to subendo location at sites of greatest hemodynamic stress and form fibrous cap
-Synthetic sm cells express scavenger receptors that can take up ox lipids and form sub pop of non macrophage foam cells

9

What growth factors do synthetic sm cells secrete?

PDGF, FGF, angiotensin II

10

Can foam cells contribute to lesion growth?

Yes, secrete all the things macrophages sec

11

What happens within the intermediate atherosclerotic lesion?

-Neo-intimal calcification (can image this)
-Remodeling (compensatory expansion with lumen occlusion)

12

Are intermediate lesions symptomatic?

Usually sub-clinical and asymptomatic but are most common lesion to cause plaque rupture at shoulder regions (large hemodynamic stress and most inflamm content)

13

Are intermediate lesions reversible?

Yes, or at least decreasable. Lipid lowering and BP control reduce CV events leading to stabilization and regression of the plaque

14

Is rupture related to vessel stenosis?

NO!

15

List the properties of a vulnerable plaque

-Thin fibrous cap
-Lots of macrophages and T cells
-Large lipid pool
-High ox LDL content
-Thin shoulder region
-Greater neovasc (brings in inflamm cells)
-Low VSMC count (vasc sm)

16

What overlapping mechanisms contribute to plaque instability?

-Impaired endoth fxn
-Thrombus formation
-Inflammation
-Impaired plaque stabilization

17

How do advanced lesions occur?

They are clinically silent and continue to grow or they rupture without clinical presentation. Some complex lesions can be contained and absorbed into an expanding lesion

18

Stage 1 of atherosclerotic lesions

Monocyte adhesion/migration

19

Stage 2 of atherosclerotic lesions

Foam cells in intima

20

Stage 3 of atherosclerotic lesions

Extracellular lipid appears (ie apoptotic macrophages release fat cells)

21

Stage 4 of atherosclerotic lesions

Core formation begins (can go straight to stage 6)
-also called atheroma lesion

22

Stage 5 of atherosclerotic lesions

Cap and core formed
-also called fibroatheroma lesion

23

Stage 6 of atherosclerotic lesions

Thrombosis

24

What is a fatty streak?

-Intracellular lipid filled foam cells
-Response to injury/inflammation
-Secrete pro-inflammatory cytokines that amplify inflammatory response

25

Within which vessels do atherosclerotic plaques form?

Elastic arteries, large and medium sized arteries

26

What are the components of a plaque?

-Cells (SMCs, macrophages, leukocytes)
-ECM (collagen, elastic fibers PGs)
-Lipid (intracellular and free)

27

What are some consequences of plaque rupture?

-Hemorrhage into the plaque
-Superimposed thrombosis due to exposure of ECM
-Aneurysmal dilation

28

What is percutaneous coronary intervention (PCI)?

Stick a balloon in the stenosis, then a stent

29

What is an unwanted consequence of PCI?

Restenosis (smc activation and constrictive remodeling)

30

Why does restenosis occur?

-The ECM is exposed due to the stress of the PCI procedure leading to platelet activation, release of cytokines and GFs
-SMcs are activated and become synthetic to secrete ECM into the intima forming a neointima within 7 days of injury
-Vascular remodeling occurs (shrinkage of lumen)-->this is what the stent stops (vessel contracts, but stent does not stop SMCs from migrating in)

31

What does PDGF do?

Induces SMC migration

32

What secretes PDGF?

Platelets, endothelial cells, macrophages, SMCs in response to vessel wall injury

33

What does basic FGF do?

induces SMC proliferation

34

What releases basic FGF?

SMCs in response to stretch or crush injury (both of which occur with PCI)

35

What is bFGF antibody?

It blocks 80% of SMC proliferation

36

What does ang II do with atherosclerosis?

Induces SMC proliferation

37

What can you give to attenuate neointimal formation?

ACE inhibitors

38

What does TGF-beta do in atherosclerosis?

ECM secretion which makes up most of the restenotic region

39

What secretes TGF beta?

SMCs, endothelial cells, and platelets following PTCA

40

What do we do to inhibit SMC proliferation after PCI?

Put drugs on the stent like rapamycin or paclitaxel that inhibits its proliferation

41

What do the stent drugs target?

They inhibit the cell cycle in some way

42

What is a dangerous complication of PCI and stents?

Late thrombosis and neointimal atherosclerosis because you mess with the endothelial cells that are req to heal the artery. This allows blood clots to form occur

43

Is restenosis predictable?

Yes, if it doesn't occur within 6 mo of procedure it prob won't

44

Name the actions of AT1 receptor

AT1 receptor is a receptor for angioII
-Vasoconstriction
-Inflammation
-Remodeling
-Thrombosis
-Inc ox stress

45

Name the actions of AT2 receptor

AT2 receptor is a receptor for angio II, less densely distributed in the body than AT1
-Vasodilation
-Reduction in inflammation
-Reduction in remodeling
-Inc NO release
-Tissue repair

46

What are the effects of angio II on atherosclerosis?

-Increases LOX-1 receptor on ECs to inc uptake of oxidized LDL
-Activates NAD(P)H oxidase which inc ROS and therefore macrophage mediated LDL activation and uptake
-EC dysfxn due to inc oxidative stress and uptake of ox LDL
-Activates NFkappaB (inc monocyte adhesion and recruitment)
-Vasoconstriction, inflammation, remodeling, thrombosis