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.
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-alpha. 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.
Horrevoets
A J
AJ
Departments of Biochemistry and Vascular Medicine of the Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. a.j.horrevoets@amc.uva.nl
Fontijn
R D
RD
van Zonneveld
A J
AJ
de Vries
C J
CJ
ten Cate
J W
JW
Pannekoek
H
H
D000595:Amino Acid Sequence; D000818:Animals; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics; D017209:Apoptosis; D001161:Arteriosclerosis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D015723:Gene Library; D006801:Humans; D017403:In Situ Hybridization; D016547:Kinesins / Q000737:chemistry / Q000235:genetics; D008075:Lipoproteins, HDL / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins; D051636:X-Linked Inhibitor of Apoptosis Protein
C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; C410089:KIF20A protein, human; D008075:Lipoproteins, HDL; D009479:Neuropeptides; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C075692:stannin; D016547:Kinesins