This document summarizes an editorial discussing a study that found erythrocyte membranes may play a role in atheromatous core formation. The study observed glycophorin-rich cores in pulmonary artery plaques from patients with chronic thromboembolic pulmonary hypertension. Glycophorins are erythrocyte membrane proteins. This suggests thromboembolic material (erythrocyte membranes) contributed to core formation. However, extrapolating these findings to coronary atherosclerosis is challenging given differences in disease etiology and timing of intraplaque hemorrhage. While erythrocyte membranes contain lipid-rich and scavenger receptor-binding constituents associated with atherosclerosis, more evidence is needed to support their direct contribution to

1. Editorial Slides
VP Watch – August 7, 2002 - Volume 2, Issue 31
The erythrocyte: an unrecognized new player in
atheromatous core formation?

2. The erythrocyte: an
unrecognized new player in
atheromatous core formation?
An editorial on Arbustini et al.
Heart. 2002 Aug;88(2):177-82.
Gerard Pasterkamp, M.D. Ph.D.

3. Background
It is generally accepted that macrophages
take up oxidized LDL via scavenger
receptors and become foam cells.
These foam cells die by necrosis or
apoptosis due to the cytotoxic effects of
internalised LDL resulting in
extracellular lipid accumulation

4. Background
• Patients with pulmonary hypertension
develop intimal plaques in large pulmonary
arteries.
• Arbustini et al. studied characteristics of
plaques obtained from pulmonary arteries of
patients that suffered from chronic
thromboembolic or plexogenic pulmonary
hypertension.

5. Results
In chronic thromboembolic pulmonary
hypertension typically atherosclerotic
plaques were observed with glycophorin
rich atheromatous cores.
Glycophorins:
Erythrocyte specific membrane protein,
sialoglycoproteins, that span the lipid bilayer
and are considered anion exchangers.

6. Conclusion of Arbustini et al.
Thromboembolic material (erythorocyte
membranes) may play a critical role in
the formation of atheromatous core
formation

7. The following figures were
generously provided by
dr E. Arbustini.

8. remodeling
Fibrous plaque with abundant
Foam cells and lymphocytes:
there is a nucleus (n)
of amorphous-pultaceous
material
n
Thrombotic material (t)
(pink-red) progressively
Trasforming in
pultecous material (p)
(gray-green)
p
t

9. Pultaceous cores immunostained by anti-glycophorin A antibodies (a and b).
c shows a vessel containing red cells (within sample positive control)

10. Coronary artery from autospy case: glycophorin A
positive pultaceous core (c); arrow indicate positive
within sample control (small new formed vessels)
c
c

11. Erythrocyt cholesterol ?
• For about 40% the weight of the
erythrocyte is composed of lipid.
• The red cell membrane is 1.5 to 2.0
times richer in cholesterol than any
other cell

12. A role for erythrocyte membrane in
atherosclerosis: is there other
circumstantial evidence?
• The sialosaccharide chains of
glycophorin A can act as ligands for
macrophage scavenger receptors (3).
• Another erythrocyte membrane
constituent has been associated with
atherosclerosis is hexacosanoate
(C26:0) which is a very long-chain fatty
acid (VLFA) (4).

13. Extrapolation from pulmonary hypertension
to coronary atherosclerosis: considerations
• Large differences in aetiology.
• Intraplaque haemorrhage is considered a late
stage event in coronary artery disease while
thromboembolic pulmonary hypertension
often revealed layered remnants of thrombi.
• Arbustini et al did not study glycophorin A
staining in coronary arteries.

14. Conclusion
• The red cell membrane hides
constituents that are lipid rich, can bind
to macrophage scavenger receptors
and are associated with risk factors for
atherosclerotic disease.
• The hypothesis that red cell
membranes contribute to atheroma
formation in coronary arteries is
challenging.

15. References
1- Arbustini E et al. Heart. 2002 Aug;88(2):177-82.
2- Pasterkamp G, Virmani R. Heart. 2002;88(2):115-6.
3- Beppu M et al Biochim Biophys Acta 1995;1268:9-19.
4- Antoku Y et al. Atherosclerosis 2000;153:169-173