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Blood, Vol. 93 No. 10 (May 15), 1999:
pp. 3418-3431
Vascular Endothelial Genes That Are Responsive to Tumor Necrosis
Factor- In Vitro Are Expressed in Atherosclerotic Lesions,
Including Inhibitor of Apoptosis Protein-1, Stannin, and Two Novel
Genes
Anton J.G. Horrevoets,
Ruud D. Fontijn,
Anton Jan van Zonneveld,
Carlie J.M. de Vries,
Jan Wouter ten Cate, and
Hans Pannekoek
From the Departments of Biochemistry and Vascular Medicine of the
Academic Medical Center, University of Amsterdam, Amsterdam, The
Netherlands.
Activation and dysfunction of endothelial cells play a prominent
role in patho-physiological processes such as atherosclerosis. We
describe the identification by differential display of 106 cytokine-responsive gene fragments from endothelial cells, activated by
monocyte conditioned medium or tumor necrosis factor- . A minority of
the fragments (22/106) represent known genes involved in various processes, including leukocyte trafficking, vesicular transport, cell
cycle control, apoptosis, and cellular protection against oxidative
stress. Full-length cDNA clones were obtained for five novel
transcripts that were induced or repressed more than 10-fold in vitro.
These novel human cDNAs CA2_1, CG12_1, GG10_2, AG8_1, and GG2_1 encode
inhibitor of apoptosis protein-1 (hIAP-1), homologues of
apolipoprotein-L, mouse rabkinesin-6, rat stannin, and a novel 188 amino acid protein, respectively. Expression of 4 novel transcripts is
shown by in situ hybridization on healthy and atherosclerotic vascular
tissue, using monocyte chemotactic protein-1 as a marker for
inflammation. CA2_1 (hIAP-1) and AG8_1 are expressed by endothelial cells and macrophage foam cells of the inflamed vascular wall. CG12_1
(apolipoprotein-L like) was specifically expressed in endothelial cells
lining the normal and atherosclerotic iliac artery and aorta. These
results substantiate the complex change in the gene expression pattern
of vascular endothelial cells, which accompanies the inflammatory reaction of atherosclerotic lesions.
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