Receptors for the anaphylatoxins C3a and C5a are expressed in human atherosclerotic coronary plaques.
The anaphylatoxins C3a and C5a are potent chemotactic and pro-inflammatory peptides that are released during complement activation, and recent clinical work have suggested them a role in acute coronary events. Here we studied whether human coronary plaques express anaphylatoxin receptors C3aR and C5aR, i.e. whether they have the potential to respond to anaphylatoxins. For this purpose, both normal (n=14) and atherosclerotic (n=20) human coronary artery samples were collected for histological and PCR analyses. Immunohistochemistry demonstrated that in atherosclerotic, but not in normal intimas, C3aR and C5aR were present. Consistently, PCR analysis showed that the expression of both receptors was >5-fold increased in the atherosclerotic plaques (p<0.01). Double immunofluorescence stainings revealed that in the plaques the principal cells expressing both C3aR and C5aR were macrophages. Moreover, T cells expressed C5aR and a small fraction of them also expressed C3aR, the mast cells expressed C5aR, whereas endothelial cells and subendothelial smooth muscle cells expressed both C3aR and C5aR. In conclusion, the presence of receptors for anaphylatoxins in human coronary plaques suggests that anaphylatoxins activate coronary plaques, and points the complement system as a potential therapeutic target in attempts to stabilize them.
Oksjoki
Riina
R
Wihuri Research Institute, Kalliolinnantie 4, FIN-00140 Helsinki, Finland.
Laine
Petri
P
Helske
Satu
S
Vehmaan-Kreula
Pirjo
P
Mäyränpää
Mikko I
MI
Gasque
Philippe
P
Kovanen
Petri T
PT
Pentikäinen
Markku O
MO
D000328:Adult; D050197:Atherosclerosis / Q000473:pathology*; D003165:Complement System Proteins; D003324:Coronary Artery Disease / Q000473:pathology*; D003331:Coronary Vessels / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D044087:Receptor, Anaphylatoxin C5a / Q000737:chemistry*; D011951:Receptors, Complement / Q000737:chemistry*
D008565:Membrane Proteins; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; C085567:complement C3a receptor; D003165:Complement System Proteins