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Complement components, but not complement inhibitors, are upregulated in atherosclerotic plaques.
K Yasojima1, C Schwab, E G McGeer
1Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver.
Arteriosclerosis, Thrombosis, and Vascular Biology
|July 14, 2001
Summary
Atherosclerotic plaques show complement activation, primarily via the classical pathway. Key complement inhibitors are not upregulated in plaques, suggesting a lack of defense against this inflammatory process.
Area of Science:
- Immunology
- Cardiovascular Biology
- Molecular Medicine
Background:
- Complement activation is implicated in the pathogenesis of atherosclerosis.
- Arterial tissue possesses complement regulatory proteins that can inhibit complement cascade.
- Understanding the balance between complement activation and inhibition in atherosclerotic plaques is crucial.
Purpose of the Study:
- To evaluate the capacity of human atherosclerotic plaques and normal arterial tissue to inhibit complement activation.
- To compare the expression of complement regulators and their targets in plaque versus normal artery.
- To determine the predominant complement pathway activated in atherosclerotic plaques.
Main Methods:
- Analysis of messenger RNA (mRNA) expression for complement inhibitors (C1 inhibitor, decay accelerating factor, CD46, C4BP, CD59) and their targets in plaque and normal arterial tissues.
- Quantitative assessment of mRNA levels using comparative ratios.
- Detection of complement activation markers (Bb fragment of factor B) using Western blotting and immunohistochemistry.
Main Results:
- All evaluated complement inhibitor mRNAs were detected in both plaque and normal arterial tissues, with no significant difference in their expression ratios.
- mRNA levels for C1r, C1s, C4, C7, and C8 were significantly increased in atherosclerotic plaques compared to normal arteries.
- The Bb fragment of factor B, a marker of alternative pathway activation, was minimally detected, indicating limited involvement of this pathway.
Conclusions:
- The classical complement pathway, not the alternative pathway, is predominantly activated in atherosclerotic plaques.
- Despite the presence of complement regulators, they are not upregulated in atherosclerotic plaques to counteract the observed complement activation.
- This imbalance suggests a potential vulnerability of atherosclerotic lesions to complement-mediated damage.