Atherogenesis process

Question 1

What can recruit monocytes

Answer 1

MCP 1
LDL entering wall
Foam cells
Activated platelets

Question 2

What damages endothelium

Answer 2

Haemodynamic stress
High LDL concentration
Smoking and other toxins
Hypertension

Question 3

What do monocytes bind to to enter intima

Answer 3

VCAM and ICAM

adhesion molecules

Question 4

What does VSCM and Foam cells lead to and what is it driven by

Answer 4

Growth factors (also activated by TGF beta)
IL-1beta, TNF alpha

Question 5

What does oxidised LDL stimulate

Answer 5

Expression of VCAM 1 and MCP 1
binds to scavenger receptors
Receptors controlling chol export down regulated - accumulation of chol esters in cytosol

Question 6

3 principal components of atherogenic plaques

Answer 6

Cells (smooth muscle cells, macrophages, T cells)
Matrix components (collagen, proteoglycans, elastic fibres)
Intracellular extracellular lipid (cholesterol and cholesterol esters)

Question 7

Dysfunctional endothelium

Answer 7

Loss of cell repellent quality
Increased permeability to lipoproteins and inflammatory cells
FUNCTIONAL

Question 8

Role of monocytes

Answer 8

Attracted by MCP-1/CCL2
Become macrophages (cytokines INF gamma, TNF a, GM-CSF, M-CSF)
Generate ROS which can oxidise LDL in intima
Produce pro-inflammatory cytokines
Express scavenger receptors

Question 9

What do endothelial cells and macrophages secrete to cause migration of VSCM into intima and what happens to VSCM

Answer 9

PDGF and TGF beta -> growth factors -> VCSM migration and proliferation
Activated VSCM synthesises ECM (collagen) and deposits it in plaque
VSCMs can become foam cells

Question 10

What does endothelial injury cause

Answer 10

Platelet adhesion, PDGF release, migration of monocytes into intima
Insudation of lipid, LDL oxidation, uptake of lipid by VSMC and macrophages
VSMC proliferation/migration