Association between complement factor H and proteoglycans in early human coronary atherosclerotic lesions: implications for local regulation of complement activation.
OBJECTIVE
Complement activation has been suggested to play a role in atherogenesis. To study the regulation of complement activation in human coronary atherosclerotic lesions, we examined the spatial relationships between the major complement inhibitor, factor H, and the complement activation products C3d and C5b-9.


RESULTS
In early lesions (American Heart Association types II and III), factor H was immunohistochemically found in the superficial proteoglycan-rich layer in association with numerous macrophages and C3d, whereas C5b-9 was found deeper in the intima, where factor H was virtually absent. In vitro experiments involving surface plasmon resonance and affinity chromatography analyses demonstrated that isolated human arterial proteoglycans bind factor H, and functional complement assays showed that glycosaminoglycans inhibit the complement activation induced by modified low density lipoprotein or by a foreign surface.


CONCLUSIONS
The present observations raise the possibility that proteoglycans, because of their ability to bind the major complement inhibitor factor H, may inhibit complement activation in the superficial layer of the arterial intima. In contrast, deeper in the intima, where factor H and proteoglycans are absent, complement may be activated and proceed to C5b-9. Thus, the superficial and the deep layers of the human coronary artery appear to differ in their ability to regulate complement activation.
Oksjoki
Riina
R
Wihuri Research Institute, Helsinki, Finland.
Jarva
Hanna
H
Kovanen
Petri T
PT
Laine
Petri
P
Meri
Seppo
S
Pentikäinen
Markku O
MO
D000328:Adult; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D002097:C-Reactive Protein / Q000032:analysis; D002846:Chromatography, Affinity; D003167:Complement Activation; D015933:Complement C3d / Q000032:analysis; D017242:Complement Factor H / Q000032:analysis / Q000378:metabolism*; D015938:Complement Membrane Attack Complex / Q000032:analysis; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D006801:Humans; D046911:Macromolecular Substances; D008264:Macrophages / Q000473:pathology; D011509:Proteoglycans / Q000032:analysis / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology
C493495:CFH protein, human; D015938:Complement Membrane Attack Complex; D046911:Macromolecular Substances; D011509:Proteoglycans; D015933:Complement C3d; D017242:Complement Factor H; D002097:C-Reactive Protein