Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Cardiology > Atherosclerosis 1 > Flashcards

Atherosclerosis 1 Flashcards

1
Q

What is atherosclerosis?

A

-arterial intimal disease of large-medium arteries characterized by lipid accumulation and inflammation in the “neo-intimal” space

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

T/F: Atherosclerosis is as acute of a disease as its clinical manifestations are.

A
  • false; it is a chronic progressive disease but with acute clinical manifestations
  • substantion accumulation of atherosclerotic plaque prior to any arterial obstruction and often with sudden rupture leading to platelet-rich thrombotic occlusion with acute MI/acute coronary syndrome (ACS) as initial presentation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Why is atherosclerosis a systemic disease?

A
  • it has wide areas of clinical consequences
    1. CHD, MI, sudden death, heart failure
    2. cerebro-vascular diseases, stroke, vascular dementia
    3. peripheral artery disease, renal artery stenosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Clinical risk factors for atherosclerosis

A
  • age and gender
  • lipoprotein disorders
  • HTN
  • DM
  • family history of premature CHD
  • smoking
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

_____________ is one of the earliest defects in the initiation of atherosclerosis.

A
  • endothelial injury and dysfunction
  • many risk factors and lifestyle behaviors (and genes) promote endothelial injury. Shear stress (HTN), circulating hormones and vasoactive pepties, as well as local cytokines, modified (oxidized, glycated) lipids and proteins mediate this process.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Ultimately, what is the underlying root of atherosclerosis?

A

-high lipids; if these are low enough, no atherosclerosis develops

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Mechanosignal transduction and hypercholesterolemia induce endothelial cell dysfunction that promotes _______ and ________ formation.

A
  • inflammation

- fatty stream formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe the process of recruitment of monocytes into the vascular wall.

A
  • activated endothelium expresses receptors that attack leukocytes and facilitate rolling, adhesion, and migration to the subendothelial space
  • selectins for rolling and VCAM,ICAM for adhesion annd MCP, oxLDL, for migration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Molecules involved in monoyte binding and recruitment to the arterial intima

A
  • endothelial adhesion mlcs: VCAM1, ICAM1, E-selectin

- chemotaxis of monocytes into subendothelium from endothelial cells and T cells: CCR2/MCP-1, CCR5, etc

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

The first step in atherosclerosis in the ___________. The second step is the _____________. What does this second step allow for? Hint: its the hallmark of the atherosclerotic lesion.

A
  • filtration of LDL from arterial lumen into arterial wall and its entrapment here
  • modification of LDL either by oxidation or chemical derivation
  • scavenger receptors on arterial wall macrophages recognize modified LDL and internalize it leading to cholesterol accumulation and ultimately to foam cell formation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

T/F: Foam cells are dynamic.

A

-true: can migrate, apoptosis or stay

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Difference in LDLR regulation in macrophage scavenger receptors. Is the native LDLR this way as well?

A
  • they are not down regulated with the intracellular accumulation of cholesterol, as other cells in the liver are
  • native LDLR is downregulated normal, the others are not.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are fatty streaks composed of?

A

-rich in cholesterol-rich foam cells and T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Modified lipoproteins, in particular LDL, play a unique role in atherosclerosis by promoting ________ while also directly contributing to ________.

A
  • inflammation

- foam cell formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Role of T Lymphocytes in atherosclerotic lesions

A
  • CD3. CD4 aBTCR+ T cells prominent in lesions, with less CD* and NK cells
  • Th1 cells dominant: express high levels of IFNy. IL12, and TNFa
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Do Th1 or Th2 T cells dominate in atherosclerotic lesions?

A
  • Th1: secrete IFNy, IL12, TNFa

- only low amts of Th2 cytokines IL4,5,10 are detected

17
Q

Actions of IL12 and IFNy in atherosclerotic lesions

A
  • Macrophages secrete IL12 which drives formation of Th1 cells
  • Th1 cells release IFNy which stimulate macrophages and cause even more IL12 release
  • IFNy also drives the migration of SMCs
18
Q

Did knockout experiments shown IL-10 to be good or bad?

A
  • good; knocking out IL10 caused worse atherosclerosis

- it is an anti-inflammatoy cytokine shown to protect against experimental atherosclerosis

19
Q

Differences in macrophage and T cell importance in atherosclerosis

A
  • Monocytes/macrophages are essential for lesion initiation and progression
  • Lymphocytes are more complex and are not obligatory for lesion initiation or progression if in the presence of hypercholesterolemia. Howevere, Th1 lymphocytes can exert a new pro-thrombotic effect unless atherogenic pressures
20
Q

In what ways are modified LDL particles similar to “bacterial infections”?

A
  • recognized as foreign and thus spur huge immune cell reactions
  • endothelial cells release cytokines and ICAMs to recruit more macrophages
21
Q

4 anti-atherogenic properties of HDL

A
  • reverse C transport from subendothelial space foam cells back into lumen where cleared by liver as bile
  • suppresses inflammatory pathways in endothelial cells, like adhesion mlcs
  • inhibits LDL modification and oxidation in subendo space
  • upregulates NO and PGI2 and suppresses thrombosis
22
Q

Macrophage foam cells, T cells, SMCs and endothelial cells release chemokines, cytokines, and growth factors that play a coordinated role in lesion progression. How?

A
  • alter SMC phenotype to synthetic and migratory
  • macrophages die and release lipids into necrotic core
  • endothelial cells die and slough off which can form thrombosis
  • fibrous cap forms but may rupture and also form thrombi
23
Q

What is responsible for the bulk increase of the lesion?

A

-medial SMC migration and proliferation with matrix secretion

24
Q

Discuss the change in phenotype of medial SMCs in atherosclerosis

A

-change from contractile quiescent form to synthetic and inflammatory form that migrates to neointima, undergoes limited proliferation, and secretes many cytokines and ECM in tissue remodeling/fibrous cap

25
Q

What are the big players in deciding if plaque is stable or not?

A
  • SMCs form fibrous cap and the more of these, the more stable plaque is
  • Inflammatory cells: T cells and Macrophages cause inflammation and MMP formation that thin out the cap.
  • balance between SMCs and inflammatory cells
26
Q

In addition to remodeling, what is another important process that occurs during intermediate atherosclerotic lesions?

A
  • Calcification within neointima
  • driven by oxLDL and inflammatory modulation of synthetic SMCs and foam cells
  • tends to emerge with lesion progression prior to development of obstructive disease or acute complications and is therefore useful imaging marker related to burder of subclinic atherosclerosis
27
Q

Glagov’s coronary remodeling process

A
  • The work they described showed that the early part of the disease was marked by plaque accumulation in the vessel wall, with subsequent enlargement of the EEM but no change in lumen size. In Glagov’s original hypothesis, plaque development is extra-luminal until the lesion occupies approximately 40% of the area within the EEM. Only then does the lumen begin to shrink.
  • remodel adventitial to accomodate initially!
28
Q

Intermediate lesions are typically subclinical and asymptomatic, But they are the typical lesion that ________.

A

-cause plaque rupture and acute clinical events
-The lesion shoulder regions are the sites of plaque rupture and erosion that precipitate acute events – these sites are under greatest hemodynamic stress and the fibrous cap at these locations in rupture prone lesions is thin and has greatest inflammatory-cell content.
Intermediate lesions may also progress slowly or sub-acutely to obstructive symptomatic lesions (e.g., angina, claudication).

29
Q

Can plaques regress?

A

yes; these are dynamic lesions that can undergo regression and stabilize – with reduction in lipid core, macrophage-foam cells and T-cells, with increased fibrous cap and fibrotic content and negative Glagov remodeling

30
Q

IFNy and cap stability

A

-IFNy from T cells stop SMC synthesis and secretion and causes release of MMPs to break down cap=rupture prone

31
Q

________ drive lesions toward more inflammatory, macrophage rich, less fibrotic lesions with SMC apoptosis.

A

-Inflammatory T cells

32
Q

Characteristics of plaques prone to rupture

A
  • thin fibrous cap
  • low VSMC count
  • large lipid pool
  • high oxLDL content
  • high macrophage content
  • high T cell cout
  • thin shoulder region
  • greater neovascularization
33
Q

T/F: Greater degree of vessel stenosis= greater risk of rupture

A
  • false; all depends on inflammatory to fibrous ratio

- most causes (70%) of acute infarct events are occluded by less than 50%; widening vessels doesn’t lead to reduce risk

34
Q

5 general components to atherosclerosis and CV events

A
  • impaired plaque stabilization
  • atherothrombotic events
  • inflammation
  • thrombus formation
  • impaired endothelial function
35
Q

When plaques rupture and cause occlusion, what is the major occlusive player?

A
  • platelets

- platelet rich thrombi!!

36
Q

How are “advanced” lesions formed?

A
  • previous ruptures that heal and do not cause clinical events
  • these get absorbed into plaque and healed over
  • Advanced obstructive lesions can occur through slow progression of intermediate lesions and inability to accommodate through Glagov remodeling. However, rapid progression to advanced lesions (e.g., with new onset angina) can occur through resolution of acute plaque rupture – not all plaque ruptures and thrombotic events result in clinical presentation. Many plaque ruptures can be silent and not progress acutely to myocardial infarction or even acute clinical presentations. Rather a plaque rupture with non obstructive thrombus is contained and absorbed into a rapidly expanded lesion. This often triggers the onset for the first time of exertional angina. Some complex lesions can show evidence of multiple plaque ruptures and old thrombotic events.
37
Q

3 ways to allow for regression of atherosclerosis

A
  1. low LDL atherogenic lipoproteins: decrease influx
  2. increased HDL or HDL function: rapid efflux
  3. regulation of macrophages and plaque inflammation: macrophage egress
38
Q

5 “kinds” of disorders atherosclerosis is

A
  1. mechanical
  2. lipoprotein
  3. inflammatory
  4. VSCMs
  5. thrombotic

Cardiology (27 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions