(Circulation. 2000;102:2185.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Overexpression of Eotaxin and the CCR3 Receptor in Human Atherosclerosis
Using Genomic Technology to Identify a Potential Novel Pathway of Vascular Inflammation
From the Respiratory Division (K.J.H., C.M.L.) and the Cardiovascular Division (J.-H.Y., Y.F., G.H.S., P.L., R.T.L.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass, and Pfizer Central Research (S.P.K., T.G.T., J.F.T.), Groton, Conn.
Correspondence to Richard T. Lee, MD, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail rtlee{at}bics.bwh.harvard.edu
Background—Unstable atherosclerotic lesions typically have an abundant inflammatory cell infiltrate, including activated T cells, macrophages, and mast cells, which may decrease plaque stability. The pathophysiology of inflammatory cell recruitment and activation in the human atheroma is incompletely described.
Methods and Results—We hypothesized that differential gene
expression with DNA microarray technology would identify new genes that
may participate in vascular inflammation. RNA isolated from cultured
human aortic smooth muscle cells treated with tumor necrosis factor-
(TNF-) was examined with a DNA microarray with 8600 genes. This
experiment and subsequent Northern analyses demonstrated marked
increases in steady-state eotaxin mRNA (>20 fold), a chemokine
initially described as a chemotactic factor for eosinophils. Because
eosinophils are rarely present in human
atherosclerosis, we then studied tissue samples from 7
normal and 14 atherosclerotic arteries. Immunohistochemical
analysis demonstrated overexpression of eotaxin protein and its
receptor, CCR3, in the human atheroma, with negligible
expression in normal vessels. Eotaxin was predominantly located in
smooth muscle cells. The CCR3 receptor was localized primarily to
macrophage-rich regions as defined by
immunopositivity for CD 68; a minority of mast
cells also demonstrated immunopositivity for
the CCR3 receptor.
Conclusions—Eotaxin and its receptor, CCR3, are overexpressed in human atherosclerosis, suggesting that eotaxin participates in vascular inflammation. These data demonstrate how genomic differential expression technology can identify novel genes that may participate in the stability of atherosclerotic lesions.
Key Words: atherosclerosis • genes • inflammation
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