Vascular endothelial genes that are responsive to tumor necrosis factor-alpha in vitro are expressed in atherosclerotic lesions, including inhibitor of apoptosis protein-1, stannin, and two novel genes
Ajg. Horrevoets et al., Vascular endothelial genes that are responsive to tumor necrosis factor-alpha in vitro are expressed in atherosclerotic lesions, including inhibitor of apoptosis protein-1, stannin, and two novel genes, BLOOD, 93(10), 1999, pp. 3418-3431
Activation and dysfunction of endothelial cells play a prominent role in pa
tho-physiological processes such as atherosclerosis. We describe the identi
fication by differential display of 106 cytokine-responsive gene fragments
from endothelial cells, activated by monocyte conditioned medium or tumor n
ecrosis factor-alpha. A minority of the fragments (22/106) represent known
genes involved in various processes, including leukocyte trafficking, vesic
ular transport, cell cycle control, apoptosis, and cellular protection agai
nst oxidative stress. Full-length cDNA clones were obtained for five novel
transcripts that were induced or repressed more than 10-fold in vitro. Thes
e novel human cDNAs CA2_1, CG12_1, GG10_2, AG8_1, and GG2_1 encode inhibito
r of apoptosis protein-1 (hIAP-1), homologues of apolipoprotein-L, mouse ra
bkine-sin-6, rat stannin, and a novel 188 amino acid protein, respectively.
Expression of 4 novel transcripts is shown by in situ hybridization on hea
lthy and atherosclerotic vascular tissue, using monocyte chemotactic protei
n-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 c
ells lining the normal and atherosclerotic iliac artery and aorta. These re
sults substantiate the complex change in the gene expression pattern of vas
cular endothelial cells, which accompanies the inflammatory reaction of ath
erosclerotic lesions. (C) 1999 by The American Society of Hematology.