Activated complement is more extensively present in diseased aortic valves than naturally occurring complement inhibitors: a sign of ongoing inflammation.
BACKGROUND
Recent studies indicate a role for complement in the pathogenesis of aortic valve disease. However, the role of naturally occurring anti-complement mediators in this context is unknown. In this study, we have analysed this in three different pathological conditions of the aortic valve: degeneration, atherosclerosis and bacterial endocarditis.


METHODS
Human aortic valves were obtained at autopsy (n = 30): 5 control valves, 10 aortic valves with atherosclerotic changes, 10 aortic valves with degenerative changes and 5 degenerative changed aortic valves with bacterial infection. These valves were analysed immunohistochemically for the presence of activated complement (C3d and C5b9) and the complement inhibitors C1-inh and clusterin. Areas of positivity were then quantified.


RESULTS
C3d, C5b9 and the complement inhibitors C1-inh and clusterin depositions were mainly found in the endothelium and extracellular matrix in aortic valves. All these mediators were already present in control valves, but the area of positivity increased significantly in response to the different diseases, with the highest increase in response to bacterial endocarditis. Interestingly, in all three aortic diseases, the depositions of complement were significantly more widespread than that of their inhibitors.


CONCLUSIONS
Our study indicates that anti-complement mediators (C1-inh and clusterin) are deposited in diseased aortic valves together with activated complement, indicating an existing counter response against complement locally in the valve. However, deposition of activated complement is significantly more widespread than that of its inhibitors, which could explain ongoing inflammation in those diseased aortic valves.
ter Weeme
M
M
OLVG, Amsterdam, The Netherlands.
Vonk
A B A
AB
Kupreishvili
K
K
van Ham
M
M
Zeerleder
S
S
Wouters
D
D
Stooker
W
W
Eijsman
L
L
Van Hinsbergh
V W M
VW
Krijnen
P A J
PA
Niessen
H W M
HW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001021:Aortic Valve / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051152:Clusterin / Q000032:analysis; D003174:Complement C1 Inactivator Proteins / Q000032:analysis; D050718:Complement C1 Inhibitor Protein; D015933:Complement C3d / Q000032:analysis; D015938:Complement Membrane Attack Complex / Q000032:analysis; D003165:Complement System Proteins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D008297:Male; D008875:Middle Aged
D051152:Clusterin; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D015938:Complement Membrane Attack Complex; C469952:SERPING1 protein, human; D015933:Complement C3d; D003165:Complement System Proteins