Atherogenesis

Question 1

Outline the stages involved in atherogenesis

Answer 1

Normal blood vessel
Fatty streak
Fibrous plaque
Occlusive athersclerotic plaque
Plaque rupture

Question 2

What is an occlusive atherosclerotic plaque

Answer 2

Plaque under endothelium composed of

1. cells (smooth muscle cells, macrophages which form foam cells and T cells)
2. Matrix components (collagen, proteoglycans, elastic fibres)
3. Intracellular and extracellular lipid (cholesterol and cholesterol esters)

Question 3

What is the role of endothelium in atherogenesis?

Answer 3

Anti-coag and anti-adhesion properties

Early dysfunction/damage is functional rather than structural

1. cell repellant quality
2. allows inflammatory cells into vascular wall
3. increased permeability to lipoproteins

Structural damages is caused by processes increasing and is observed later in atherogenic process

Question 4

What is the role of monocytes in atherogenesis?

Answer 4

Attracted to developing plaques by MCP-1/CCL2

Transform into macrophages under influence of cytokines (IFN-y, TNF-a, GM-CSF, M-CSF) secreted by endothelium and vascular smooth muscle cells (VSMC)

Generate ROS which can oxidise LDL in intima

Produce pro-inflammatory cytokines

Express scavenger receptors

Question 5

Describe lipid involvement in atherogenesis

Answer 5

Remnants and LDL enter vascular wall more easily than other particles
Can be oxidised in the intimate (by oxidases from macrophages and ROS from VSMC)

Question 6

What is the role of VCAM1?

Answer 6

Pulls monocytes form circulation into plaque

Question 7

What is the role of oxidised LDL in atherogenesis?

Answer 7

Stimulates expression of VCAM-1 and MCP-1 which directs monocytes/macrophages into lesion

Oxidised B-100 binds to scavenger receptor on macrophages and is phagocytosed

No feedback regulation via cholesterol concentration

Generation of foam cells which are visible in arterial walls as fatty streaks

Question 8

Describe how the migration of VSMCs contributes to this process

Answer 8

Responsible for structure of vessel wall

Endothelial cells and macrophages secrete PDGF and TGF-Beta
Effect on VSMC: they proliferate and migrate into intima

Activates VSMCs also synthesise ECM (collagen) which deposit in plaque

Migrating cells and deposits of ECM material all disrupt structure of vessel wall

Question 9

Describe the differences between stable and vulnerable plaques

Answer 9

Stable
Thick fibrous cap 
Increases VSMC and collagen
Small lipid pool
Few inflammatory cells

Vulnerable
Thin fibrous cap (less collagen)
Low VSMC content
Large lipid pool
Many inflammatory cell
Necrotic core