Editorial Slides VP Watch – August 7, 2002 - Volume 2, Issue 31

The erythrocyte: an unrecognized new player in atheromatous core formation?

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.

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

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.

ResultsIn 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.

Conclusion of Arbustini et al.

Thromboembolic material (erythorocyte membranes) may play a critical role in

the formation of atheromatous core formation

The following figures were generously provided by

dr E. Arbustini.

remodelingFibrous plaque with abundantFoam 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

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

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

c

c

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

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).

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.

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.

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