Atherosclerosis

Question 1

Atherosclerosis

Answer 1

a disease of the arteries characterized by the deposition of fatty material on their inner walls.

Question 2

What stage are the inner vessel walls at during the first decade of atherosclerosis

Answer 2

Foam cells > fatty streak

Question 3

What stage are the inner vessel wall at during the third decade of atherosclerosis

Answer 3

Intermediate lesion > atheroma

Question 4

What stage are the inner vessel walls at during the fourth decade of atherosclerosis

Answer 4

Fibrous plaque > complicated lesion/rupture
(Smooth muscle collagen. Thrombosis hematoma)

Question 5

What stage of atherosclerosis is clinically silent

Answer 5

Fatty streak

Question 6

What stage of atherosclerosis causes temporary symptoms

Answer 6

Fibrous plaque

Question 7

What stage of atherosclerosis causes permanent damage

Answer 7

Plaque rupture/thrombosis

Question 8

What vessels are susceptible to atheroma formation

Answer 8

Despite systemic nature of many risk factors, arterial areas subject to either disturbed flow or low shear stress have particular susceptibility to atheroma formation

Question 9

Three layers of arterial wall

Answer 9

Tunica externa (collagen), tunica media (smooth muscle), tunica intima (endothelium + ECM)

The tunica media is separated off by ex/internal elastic membrane

Question 10

What are the components of the fibrous cap

Answer 10

Smooth muscle cells, macrophages, foam cells, lymphocytes, collagen, elastin, proteoglycans, neovascularization.

Question 11

Components of the necrotic centre

Answer 11

Cell debris, cholesterol crystals, foam cells, calcium

Question 12

How does thrombosis occur

Answer 12

Rupture of fibrous cap allows contact between blood and thrombogenic lipid core platelet aggregation and thrombus formation occludes arterial lumen

Question 13

What are lipoproteins

Answer 13

Particles made of proteins and fats that transport cholesterol and other lipids through blood cells.

Question 14

What are foam cells

Answer 14

Macrophages that localise to fatty deposits and ingest low density lipoproteins and become loaded with lipids.

Question 15

Role of nitric oxide in endothelial cells

Answer 15

Small, soluble gas with vasodilatory, anti-inflammatory, and antioxidant properties that play a role in the maintenance of vascular homeostasis

Question 16

What causes rupture of fibrous cap

Answer 16

The combination of increased mechanical stress on the fibrous cap and weakening of the fibrous cap extracellular matrix leads to plaque rupture.

Question 17

What causes rupture of fibrous cap

Answer 17

The combination of increased mechanical stress on the fibrous cap and weakening of the fibrous cap extracellular matrix leads to plaque rupture.

Question 18

In what form do lipids circulate

Answer 18

Free cholesterol, cholesterol ester, triglycerides, and phospholipids

Question 19

What is the precursor of steroid hormones and bile acids

Answer 19

Lipids

Question 20

Describe the mechanism of endocytosis of lipoproteins

Answer 20

Lipoprotein binds to lipoprotein receptor and enters forming Claritin coated pit.
Receptor detaches and is recycled to membrane.
Endosome becomes lysosome

Question 21

Explain the mechanism of transcytosis of lipoprotein

Answer 21

Recognition of LDL at caveolae which is rich in scavenger receptors, SR-B1 and ALK1 which activate the rac system which allows for the formation of an endosome that can travel from the apical to the base side of the endothelial cell.

Question 22

What is LOX-1

Answer 22

An oxLDL (scavenger) receptor
Epithelial cell: apoptosis, oxLDL uptake, endothelial injury, monocyte adhesion, senescence

Question 23

What is the difference between athero-prone and athero-protected endothelial membranes

Answer 23

In athero-prone regions, the distal flow increases the formation of caveolae and increases the contact of LDL with caveolae

Laminar flow decreases the contact of LDL with caveolae

Question 24

How are macrophages foam cells formed

Answer 24

Uptake of oxLDL by macrophages
Once inside, oxLDL is broken down and free cholesterol and fatty acids are released, the macrophages accumulate these lipids forming lipid droplets.

Question 25

What parts of the extra cellular matrix increase plaque stability

Answer 25

Collagens, proteoglycans, elastin, lamnins

Question 26

Examples of lipid lowering drugs

Answer 26

Statins, PCSK9-inhibitors

Question 27

Examples of anti-inflammatory agents

Answer 27

Camakinumab

Question 28

Antioxidant used to treat atherosclerosis

Answer 28

Vitamin E

Question 29

Why is LDL bad and HDL good

Answer 29

LDL is more likely to oxidise
HDL has different proteins and enzymes that help prevent oxidation and protect cells from damage caused by oxidised LDL

Question 30

What does oxidised LDL do

Answer 30

Inhibits activity of nitric oxide synthase and also nitric oxide production by endothelial cells
Can trigger expression of adhesion molecules from the cell surface and also stimulate activation of epithelial cells

Question 31

Statins mechanism of action

Answer 31

Block HMG-CoA reductase which stops the me all are pathway and inhibits cholesterol formation

Question 32

Pleiotropic effects of statins

Answer 32

New onset type 2 diabetes
Protein glycosylation and folding
Satin induced myopathies
Neurological conditions

Question 33

Mechanism of action of PCSK9

Answer 33

•PCSK9 binds the LDL receptor (LDLR)
●Targets LDLR for lysosomal degradation
●Reduces LDL uptake by hepatocytes
●Increases Circulating LDL