doi: 10.1161/hq0701.092160
© 2001 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Complement Components, but Not Complement Inhibitors, Are Upregulated in Atherosclerotic Plaques
From the Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver.
Correspondence to Dr Patrick L. McGeer, Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC V6T 1Z3. E-mail mcgeerpl{at}interchange.ubc.ca
Abstract—Complement activation occurs in atherosclerotic plaques. The capacity of arterial tissue to inhibit this activation through generation of the complement regulators C1 inhibitor, decay accelerating factor, membrane cofactor protein (CD46), C4 binding protein (C4BP), and protectin (CD59) was evaluated in pairs of aortic atherosclerotic plaques and nearby normal artery from 11 human postmortem specimens. All 22 samples produced mRNAs for each of these proteins. The ratios of plaque versus normal artery pairs was not significantly different from unity for any of these inhibitors. However, in plaques, the mRNAs for C1r and C1s, the substrates for the C1 inhibitor, were increased 2.35- and 4.96-fold, respectively, compared with normal artery; mRNA for C4, the target for C4BP, was elevated l.34-fold; and mRNAs for C7 and C8, the targets for CD59, were elevated 2.61- and 3.25-fold, respectively. By Western blotting and immunohistochemistry, fraction Bb of factor B, a marker of alternative pathway activation, was barely detectable in plaque and normal arterial tissue. These data indicate that it is primarily the classical, not the alternative pathway, that is activated in plaques and that key inhibitors are not upregulated to defend against this activation.
Key Words: CD59 • CD46 • C4 binding protein • classical pathway • inflammation
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