Atherosclerosis Flashcards

1
Q

What are the modifiable risk factors of atherosclerosis?

A

Smoking, lipid intake, blood pressure, diabetes, obesity, sedentary lifestyle

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2
Q

What are the non-modifiable risk factors for atheroslcerosis?

A

Age, sex, genetic background

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3
Q

What changes in the risk factors associated with atherosclerosis have occurred in the last decade and how is this effecting the epidemiology of atherosclerosis?

A

Reduced hyperlipidaemia and reduced hypertension. However increase obesity and increased diabetes so increase in atherosclerosis

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4
Q

Atherosclerosis is mainly a disease of which vessels?

A

Medium and large arteries particularly at bifurcations as the turbulent flow creates vortexes setting up inflammatory changes

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5
Q

How does inflammation allow LDL deposit?

A

LDLs deposit in between endothelium and internal elastic laminate and bind to matrix proteoglycans

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6
Q

What are the give main cell types involved in atherosclerosis?

A

Vascular endothelial cells, monocyte-macrophages, platelets, vascular smooth cell muscle cells, T lymphocytes

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7
Q

What is the role of vascular endothelial cells in atherosclerosis?

A

Barrier function e,g to lipoproteins, leukocyte recruitment.

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8
Q

How are monocyte-macrophages involved in atheroslcerosis?

A

Accumulate fat from blood. Involved in foam cell formation. Cytokine and growth factor release. Major source of free radicals. Metalloproteinases

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9
Q

What is the role of platelets in atherosclerosis?

A

Thrombus generation. Cytokine and growth factor release

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10
Q

What is the role of vascular smooth muscle cells in atherosclerosis?

A

Migration and proliferation. Collagen synthesis. Remodelling and fibrous cap formation

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11
Q

What is the role of T lymphocytes in atherosclerosis?

A

Macrophage activation. Macrophage de-activation. VSMC death. B-cell/antibody help

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12
Q

What is the main inflammatory cell involved in atherosclerosis?

A

Macrophages, kill microorganisms at the expense of the host tissue

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13
Q

Is atherosclerosis purely an inflammatory disease?

A

Has an inflammatory basis however multiple mechanisms such as cholesterol crystal formation contribute

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14
Q

What effects does injection of antibodies to IL-1 have on patients at high risk of atherosclerosis? What does this prove?

A

Have fewer major adverse cardiovascular events, proves inflammatory basis

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15
Q

How are macrophage subtypes regulated?

A

By combinations of transcription factors binding to regulatory sequences on DNA however not yet understood

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16
Q

How is the world disease burden for atherosclerosis changing?

17
Q

Which of the following statement is CORRECT for atherosclerosis ?
A: It is decreasing globally due to improved lifestyle
B: It is an inflammatory disease of arteries characterised by macrophage inflammatory cells
C: It is characterised by proliferation of pericytes, which drive the disease via IL-15
D: Anti-inflammatory treatments such as anti-IL-1 have no effect as it is solely driven by ageing and telomere shortening
E: It only affects coronary arteries making it the specialty interest of cardiologists

A

B: It is an inflammatory disease of arteries characterised by macrophage inflammatory cells

18
Q

Which of the following statement is CORRECT for atherosclerotic risk factors?
A: Are expected to decrease globally leading to a decrease in cardiovascular disease worldwide
B: Include high blood pressure, diabetes, hyperlipidaemia, smoking, age, and anatomically localising branches and bends
C: Are not worth treating since atherosclerosis is fundamentally a degenerative disease
D: Do not modify vascular and leukocyte cell functions because they promote arterial thickening by the fatberg mechanism (passive deposition at branches and bends)
E: Do not interact in any meaningful way, consequently integrated risk factor management is without any basis

A

B: Include high blood pressure, diabetes, hyperlipidaemia, smoking, age, and anatomically localising branches and bends

19
Q

what is LDL?

A

low density lipoprotein. synthesised in the liver. carries cholesterol from the liver to rest of the body including arteries

20
Q

what is HDL?

A

high density lipoprotein. good cholesterol, carries cholesterol from peripheral tissues including arteries back to liver

21
Q

what are oxidised LDLs?

A

chemical and physical modifications of LDL by free radicals, enzymes and aggregation form a family of highly inflammatory and toxic forms of LDL found in vessel walls

22
Q

outline the process of modification of subendothelial trapped LDL

A

LDLs leak through the endothelial barrier. is trapped by binding to sticky matrix carbohydrates in the sub-endothelial layer and becomes susceptible to modification. oxidation - free radical attack from activated macrophages

23
Q

what is familial hyperlipidaemia?

A

autosomal genetic disease with characteristic massively elevated cholesterol due to failure to clear LDL from blood

24
Q

What is the characteristic sign of familial hyperlipidaemia?

A

xanthoma (foam cells)

25
what happens if familial hyperlipidaemia is left untreated?
fatal myocardial infarction before age 20
26
true or false: both macrophage receptors bind to LDL and dead cells?
true
27
what are the two types of macrophage receptor involved in LDL?
scavenger receptors A and B
28
what is macrophage scavenger receptor A?
known as CD204, binds to oxidised LDL, gram +ve bacteria and dead cells.
29
what is macrophage scavenger receptor B?
known as CD36, binds to oxidised LDL, binds to malaria parasites and dead cells
30
what effect does cellular cholesterol have on cholesterol synthesis and what did this help in the discovery of?
Cholesterol synthesis is also negatively regulated by cellular cholesterol. Helped the discovery of HMG-CoA reductase inhibitors (= “statins”) for lowering plasma cholesterol.
31
what is the function of PCSK9 inhibitors?
PCSK9 degrades LDLR •LDLR removes cholesterol from blood and allows it to suppress cholesterol biosynthesis •PCSK9-deficient humans are protected from cardiovascular disease
32
In severe or statin-resistant hyperlipidaemia, what is given?
PCSK9 inhibitors
33
What is the effect on macrophages of LDLR-negative patients?
Accumulate cholesterol