This document introduces a hypothesis that spatial heterogeneity within plaques may provide information about regional mechanisms independent of classical risk factors. It aims to use a new 3D histology technique to provide evidence that local accumulation of lipids activates inflammatory cells to produce plaque-weakening factors. Graphs show measurements of plaque area, macrophage density, lipid density, smooth muscle cell density, and a vulnerability index at different distances from the renal artery.

1. Does spatial heterogeneity of
(experimental) plaques contain
information

2. Introduction
• Plaque rupture occurs predominantely
upstream of plaques in carotid artery
• Vulnerable plaque occurs at first 30 cm of
coronary arteries

3. Hypothesis
• This heterogeneity may help to identify us
with regional mechanism independent of
classical risk factors

4. Aim
• Introduce a new 3D histology technique
• Provide evidence for the mechanism that
local accumulation of lipids activates
inflammatory cells to produce plaque
weakoning factors

6. oxLDL Macrophages MMPs SMC

7. 50403020100
x106
Distance from Renal Artery (mm)
0
1
2
3
PlaqueArea(µm2
)
Plaque Area
Distance from Renal Artery (mm)
5
1
0
1
5
0
50403020100
Density(%)
Macrophages
60
50403020100
40
20
Density(%)
Distance from Renal Artery (mm)
Lipids
0
60
50
40
30
20
10
0
50403
0
2
0
100
Density(%)
Distance from Renal Artery (mm)
Smooth Muscle Cells

8. 0
5
10
15
20
25
50403020100
Distance from Renal Artery (mm)
VI-index
Plaque area
VI-index

9. A
C D
B

10. oxLDL distibutionMMP activity
smcsmc
mac
mac
MMP-activity Ox-LDL accumulation
unknown
unknown

11. A
B