Lecture 16: Atherogenesis

Question 1

what is the first sign of atherogenesis visible without magnification?

Answer 1

Fatty streaks

Question 2

Where do atherogenic plaques develop?

Answer 2

In the tunica intima

Question 3

What causes atherogenic plaques to build up int he tunica intima?

Answer 3

The migration of cells from the tunica media and the recruitment of leukocytes from the blood

Question 4

What are the three main components of an atherogenic plaque?

Answer 4

1: cells (smooth muscle cells, macrophages (foam cells), T cells)
2: matrix components (collagen, proteoglycans, elastic fibres)
3: intracellular and extracellular lipid (cholesterol and cholesterol esters)

Question 5

What is produced by the endothelium to cause vasorelaxation?

Answer 5

NO

Question 6

What are the effects of NO on the blood vessel?

Answer 6

Vasorelaxation, anti-adhesion, prevents platelet activation and neutrophil recruitment

Question 7

Is the early dysfunction of the endothelium structural or functional?

Answer 7

Functional

Question 8

What attracts monocytes to the developing plaques?

Answer 8

MCP1

Question 9

What causes monocytes to transform into macrophages?

Answer 9

Cytokines (IFN-gamma, TNF-alpha, GM-CSF, M-CSF) secreted by the endothelium and vascular smooth muscle cells

Question 10

What oxidises LDL in the intima?

Answer 10

Reactive oxygen species (ROS) from macrophages and VSMCs

Question 11

What are the pro-inflammatory cytokines produced by monocytes/macrophages?

Answer 11

IL1, Il6 and TNFa

Question 12

What type of receptors are expressed on the surface of monocytes/macrophages?

Answer 12

Scavenger receptors

Question 13

Oxidised LDL stimulates the expression of what to direct macrophages to the sites of lesions?

Answer 13

VCAM1 and MCP1

Question 14

What bind the scavenger receptors on macrophages?

Answer 14

Oxidised B-100 (it is then phagocytosed)

Question 15

What happens to the receptors controlling cholesterol export when LDL is recognised by scavenger receptors rather than the LDL receptors?

Answer 15

They are down regulated

Question 16

What type of cells secrete PDGF and TGF-b?

Answer 16

Endothelial cells and macrophages

Question 17

What is the effect of secretion of PDGF and TGF-b?

Answer 17

Proliferation of VSMCs and their migration into the intima

Question 18

Which cells synthesise ECM?

Answer 18

VSMCs

Question 19

Which cells become foam cells?

Answer 19

Macrophages and VSMCs

Question 20

What are the key features of a vulnerable plaque?

Answer 20

Thin fibrous cap
Large lipid pool
Many inflammatory cells
Low VSMC content

Question 21

What are the key features of a stable plaque?

Answer 21

Thick fibrous plaque
Small lipid pool
Few inflammatory cells
High VSMC content

Question 22

What is the definition of familial hypercholesterolaemia?

Answer 22

Genetic disorder of genes related to LDL metabolism resulting in lifelong elevation of LDL-C

Question 23

What may cause endothelial injury?

Answer 23

Raised LDL

‘Toxins’ eg cigarette smoke

Hypertension

Haemodynamic stress

Question 24

What is caused by endothelial injury?

Answer 24

Platelet adhesion, PDGF release, migration of monocytes into intima

Insudation of lipid, LDL oxidation, uptake of lipid by VSMC and macrophages

VSMC proliferation and migration

Question 25

Name a natural statin.

Answer 25

Lovastatin (mevacor), Compactin, Pravastatin (pravachol), Simvastatin (Zocor).

Question 26

Name a synthetic statin.

Answer 26

Atorvastatin (Lipitor), Fluvastatin (Lescol)