Lec 14 Atherosclerosis Flashcards Preview

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Flashcards in Lec 14 Atherosclerosis Deck (46):
1

What is role of endothelial cells in normal vascular homeostasis?

- physical barrier to large molec
- secrete substances that are anti-inflammatory and promote vasodilation [NO] and resist thrombosis

= maintains homeostasis

2

What is role of smooth muscle cells in normal vascular homeostasis?

- effect vasoconstriction/ vasodilation in response to local/circulating molec = maintain vascular tone
- produce extracellular matrix to maintain vascular integrity
- contained within arterial media

3

What is role of collagen and elastin?

collagen maintains strength
elastin maintains flexibility

both produced by smooth muscle cells

4

What are the 3 layers of normal arterial wall?

intima = closest to lumen, consists of single layer endothelial cells

media = middle, bounded by elastin [internal and external elastic laminae], consists of smooth muscle cells and extracellular matrix

adventitia = outer, contains nerves, lymphatics, blood vessels

5

What makes up the extracellular matrix?

collagen + elastin + proteoglycans

maintain structural integrity of vessel

6

What is the earliest visible lesion of atherosclerosis?

fatty streak

7

What is the order:
plaque disruption
fatty streak
plaque progression

fatty streak --> plaque progression --> plaque disruption

8

What is mech/pathway of fatty streak?

- endothelial cell dysfunction: endothelial cell no longer physical barrier

- increased endothelial permeability allows entry LDL into intima where it stays in subendothelial space

- LDL gets modified [by oxidation or glycation] = mLDL

- mLDL promotes leukocyte recruitment and foam cell formation] + stimulates inflammation directly + indirectly

- recruitment leukocytes [monocytes + T cells] to vessel wall

- monocytes into intima --> become phagocytes --> take up mLDL to become foam cells via unregulated scavenger receptor

- foam cell apoptosis, necrosis, persistent inflammation = make up core of plaque formation

9

What are risk factors for initial endothelial cell dysfunction that leads to fatty streak/atherosclerosis formation?

smoking, high cholesterol, diabetes

associated with hydrodynamic stress --> high BP, branch points in vessels

10

How does mutated apolipoprotein B lead to atherosclerosis?

b/c it allows easier entry of LDL into the subendothelial space

11

What is the necrotic core?

lipid rich center of a plaque formed by necrotic foam cells

12

When do fatty streaks appear?

start to appear in early life, by late teens can be found but are asymptomatic

13

What is mech/pathway of plaque progression?

-

14

What happens in early plaque growth?

have outward remodeling of arterial wall to preserve diameter of lumen and does not limit blood flow so you don't get ischemic symptoms

15

What happens in later plaque growth?

over time vessel can no longer compensate with outward remodeling --> start to restrict vessel lumen and impede perfusion --> tissue ischemia --> symptoms like angina or claudication of extremities

16

What is underlying pathology of most coronary syndromes?

fibrous cap of an atherosclerotic plaque ruptures --> exposes prothrombic molec within lipid core and precipitates actual thrombus that occludes arterial lumen

17

What is mech/pathways of plaque progression from fatty streak to fibrous plaque?

- smooth muscle cells migrate from arterial media into intima and proliferate [signaled by foam cells, platelets, endothelial cells]

- smooth muscle cells secrete collagen/extracellular matrix to form fibrous cap on plaque

- T-lymphocyte IFN-g inhibits smooth muscle collagen synthesis + local foam cells secrete MMP both degrade fibrous cap

- balance betwen cap degradation in synthesis results in stable vs vulnerable plaque

18

What are characteristics of stable vs vulnerable plaque?

stable = small lipid pool thick fibrous cap, preserved arterial lumen

vulnerable = large lipid cores, thin fibrous cap, many inflammatory cells

19

What happens in plaque disruption?

- fibrous cap ruptures due to hemodynamic stress and matrix degradation

- subsequent development of superimposed thrombus consisting of fibrin, RBCs, platelets

- clinical manifestion depends on vascular territory and stability of overlying thrombus = rupture may heal and just narrow lumen [=silent] or may cause complete occlusion and major event [ex. MI]

20

Why higher risk of MI in the morning?

higher BP in the morning = more hemodynamic stress = more likely to plaque to rupture

21

What is order of location where atherosclerotic plaques happen first?

step1

ab aorta > coronary aorta > popliteal artery > carotid artery

22

What are traditional non-modifiable risk factors of atherosclerosis?

step1

- age [older]
- gender [male or post-menopausal female]
- family history

23

What are modifiable risk factors for atherosclerosis?

step1

- smoking
- hypertension
- hyperlipidemia
- diabetes
- physical inactivity

24

What are gender risk factors for atherosclerosis?

step1

higher risk in men and in post-menopausal women

25

What are symptoms of atherosclerosis?

step1

angina
claudication = pain in legs in exercise due to insufficient blood flow
or can be asymptomatic

26

How does risk of cardiovascular disease increase with age?

linearly

27

What is difference high vs low density lipoprotein?

higher density = bigger ration proteins:lipids

higher density = less bad

28

What is structure of lipoproteins?

- lipid core of cholesteryl esters and triglycerides
- surrounded by hydophilic phospholipid/protein/cholesterol layer

29

What does LDL do?

= bad cholesterol
- deposits cholesterol in subendothelial space leading to atherosclerosis

30

What does HDL do?

= good cholesterol
- reverses cholesterol transport
- takes cholesterol from macrophages in subendothelial space and brings it back to liver to be processes

31

What is synergism of HDL and LDL risk factors for atherosclerosis?

pts with low HDL and high LDL have triple risk of those on opposite end of spectrum

low HDL + high LDL is worse than either risk factor alone

32

What is non-pharm mech for lowering LDL?

diet/exercise

33

How do you medically lower LDL?

give statins = HMG-CoA reductase inhibitors

- increase expression of LDL receptor in liver so lower serum LDL

34

What is effect of statins of cardiovascular resik?

- benefit proportional to degree of LDL lowering

- also has some elevation in HDL

35

What are the non-LDL lowering mech of statins?

- modulate vascular tone [dilate]
- stabilize plaque
- reduce inflammation
- rase HDL a little

36

What are the major risk factors that affect LDL level?

- cigarette smoking
- hypertension
- low HDL
- family history of premature coronary heart disease
- age

37

What is effect of DM on cardiovascular?

accelerates atherosclerosis + puts you in prothrombotic state

38

Who has same risk "risk equivalent" for CHD as a diametic without prior MI?

a normal pt with a prior MI

39

What are treatment objectives in diabetic pt?

preven microvascular complications [nephropathy, neuropathy, retinopathy] by glycemic control

prevent macrovascular [stroke, MI] by control of midfiable cardiac risk factors

40

Why does obesity put you at risk for vascular events?

- more adipose tissue --> secretes pro-inflammatory cytokines

-higher BP --> higher CO to meat higher metabolic demands

- endothelial dysfunction

- insulin resistance

41

What is obesity?

BMI > 30

42

What is the physical activity recommendation?

Every US adult should accumulate 30 minutes or more of moderate-intensity physical activity on most, preferably all, days of the week

43

What is effect of smoking on vasculature?

causes endothelial damages, platelets more aggregable [prothrombic]

44

What is role of homocystein in atherogenesis?

CVD pts have high levels homocysteine but reductions don't benefit CV risk

45

What is lipoprotein A?

variant of LDL
may impair endogenous thrombolysis + promote inflammation

people with high lipoprotein A have higher CV risk

46

What is c reactive protein role in atherogenesis?

marker of inflammation and associated wtih increased CV risk

unclear if marker or mediator of atherosclerosis