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Generation of C-reactive protein and complement components in atherosclerotic plaques.
- Source :
-
The American journal of pathology [Am J Pathol] 2001 Mar; Vol. 158 (3), pp. 1039-51. - Publication Year :
- 2001
-
Abstract
- C-reactive protein (CRP) and complement are hypothesized to be major mediators of inflammation in atherosclerotic plaques. We used the reverse transcriptase-polymerase chain reaction technique to detect the mRNAs for CRP and the classical complement components C1 to C9 in both normal arterial and plaque tissue, establishing that they can be endogenously generated by arteries. When the CRP mRNA levels of plaque tissue, normal artery, and liver were compared in the same cases, plaque levels were 10.2-fold higher than normal artery and 7.2-fold higher than liver. By Western blotting, we showed that the protein levels of CRP and complement proteins were also up-regulated in plaque tissue and that there was full activation of the classical complement pathway. By in situ hybridization, we detected intense signals for CRP and C4 mRNAs in smooth muscle-like cells and macrophages in the thickened intima of plaques. By immunohistochemistry we showed co-localization of CRP and the membrane attack complex of complement. We also detected up-regulation in plaque tissue of the mRNAs for the macrophage markers CD11b and HLA-DR, as well as their protein products. We showed by immunohistochemistry macrophage infiltration of plaque tissue. Because CRP is a complement activator, and activated complement attacks cells in plaque tissue, these data provide evidence of a self-sustaining autotoxic mechanism operating within the plaques as a precursor to thrombotic events.
- Subjects :
- Aged
Arteries metabolism
Arteries pathology
Arteriosclerosis metabolism
Arteriosclerosis pathology
Blotting, Western
C-Reactive Protein biosynthesis
Complement System Proteins biosynthesis
Female
HLA-DR Antigens biosynthesis
HLA-DR Antigens genetics
Humans
In Situ Hybridization
Macrophage-1 Antigen biosynthesis
Macrophage-1 Antigen genetics
Macrophages metabolism
Male
Muscle, Smooth, Vascular metabolism
RNA, Messenger biosynthesis
Transcriptional Activation
Up-Regulation
Arteriosclerosis genetics
C-Reactive Protein genetics
Complement System Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0002-9440
- Volume :
- 158
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The American journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 11238052
- Full Text :
- https://doi.org/10.1016/S0002-9440(10)64051-5