Atherosclerosis

Question 1

What are the modifiable risk factors of atherosclerosis?

Answer 1

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

Question 2

What are the non-modifiable risk factors for atheroslcerosis?

Answer 2

Age, sex, genetic background

Question 3

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

Answer 3

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

Question 4

Atherosclerosis is mainly a disease of which vessels?

Answer 4

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

Question 5

How does inflammation allow LDL deposit?

Answer 5

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

Question 6

What are the give main cell types involved in atherosclerosis?

Answer 6

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

Question 7

What is the role of vascular endothelial cells in atherosclerosis?

Answer 7

Barrier function e,g to lipoproteins, leukocyte recruitment.

Question 8

How are monocyte-macrophages involved in atheroslcerosis?

Answer 8

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

Question 9

What is the role of platelets in atherosclerosis?

Answer 9

Thrombus generation. Cytokine and growth factor release

Question 10

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

Answer 10

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

Question 11

What is the role of T lymphocytes in atherosclerosis?

Answer 11

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

Question 12

What is the main inflammatory cell involved in atherosclerosis?

Answer 12

Macrophages, kill microorganisms at the expense of the host tissue

Question 13

Is atherosclerosis purely an inflammatory disease?

Answer 13

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

Question 14

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

Answer 14

Have fewer major adverse cardiovascular events, proves inflammatory basis

Question 15

How are macrophage subtypes regulated?

Answer 15

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

Question 16

How is the world disease burden for atherosclerosis changing?

Answer 16

is rising

Question 17

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

Answer 17

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

Question 18

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

Answer 18

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

Question 19

what is LDL?

Answer 19

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

Question 20

what is HDL?

Answer 20

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

Question 21

what are oxidised LDLs?

Answer 21

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

Question 22

outline the process of modification of subendothelial trapped LDL

Answer 22

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

Question 23

what is familial hyperlipidaemia?

Answer 23

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

Question 24

What is the characteristic sign of familial hyperlipidaemia?

Answer 24

xanthoma (foam cells)

Question 25

what happens if familial hyperlipidaemia is left untreated?

Answer 25

fatal myocardial infarction before age 20

Question 26

true or false: both macrophage receptors bind to LDL and dead cells?

Answer 26

true

Question 27

what are the two types of macrophage receptor involved in LDL?

Answer 27

scavenger receptors A and B

Question 28

what is macrophage scavenger receptor A?

Answer 28

known as CD204, binds to oxidised LDL, gram +ve bacteria and dead cells.

Question 29

what is macrophage scavenger receptor B?

Answer 29

known as CD36, binds to oxidised LDL, binds to malaria parasites and dead cells

Question 30

what effect does cellular cholesterol have on cholesterol synthesis and what did this help in the discovery of?

Answer 30

Cholesterol synthesis is also negatively regulated by cellular cholesterol. Helped the discovery of HMG-CoA reductase inhibitors (= “statins”) for lowering plasma cholesterol.

Question 31

what is the function of PCSK9 inhibitors?

Answer 31

PCSK9 degrades LDLR
•LDLR removes cholesterol from blood and allows it to suppress cholesterol biosynthesis
•PCSK9-deficient humans are protected from cardiovascular disease

Question 32

In severe or statin-resistant hyperlipidaemia, what is given?

Answer 32

PCSK9 inhibitors

Question 33

What is the effect on macrophages of LDLR-negative patients?

Answer 33

Accumulate cholesterol