Endothelial Specificity of ICAM2, Flt-1, and Tie2 Promoters In Vitro and In Vivo
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 32769
Endothelial Specificity of ICAM2, Flt-1, and Tie2 Promoters In Vitro and In Vivo

Authors: Jing Lei, Yoram Vodovotz, Timothy R. Billiar

Abstract:

To identify an endothelial cell-specific promoter suitable for vascular-specific targeting, we tested five promoters in vitro--Tie2SE, Tie2LE, ICAM2, Flt-1 and vWF--for promoter activity and specificity in endothelial cells, smooth muscle cells and non-vascular resident cells as well as tissues. These promoters, except for vWF, exhibited good endothelial activity and specificity in vitro. In a syngenic heart transplantation model, the ICAM2 promoter was variably functional in coronary endothelial cells of donor hearts. Thus, the ICAM2, Flt-1, Tie2SE and Tie2LE promoters hold promise for endothelial-specific targeting, but in vitro expression may not predict in vivo expression.

Keywords: vascular-specific targeting, endothelial cell-specificpromoter, endothelial specificity.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1330647

Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 2388

References:


[1] Hajitou A, Pasqualini R, Arap W. Vascular targeting: recent advances and therapeutic perspectives. Trends Cardiovasc Med. 16 (2006) 80-88.
[2] Schlaeger TM, Bartunkova S, Lawitts JA, Teichmann G, Risau W, Deutsch U, Sato TN. Uniform vascular-endothelial-cell-specific gene expression in both embryonic and adult transgenic mice. Proc Natl Acad Sci U S A 94 (1997) 3058-3063.
[3] Cowan PJ, Shinkel TA, Witort EJ, Barlow H, Pearse MJ, d'Apice AJ. Targeting gene expression to endothelial cells in transgenic mice using the human intercellular adhesion molecule 2 promoter. Transplantation 62 (1996) 155-60.
[4] Aird WC, Jahroudi N, Weiler-Guettler H, Rayburn HB, Rosenberg RD. Human von Willebrand factor gene sequences target expression to a subpopulation of endothelial cells in transgenic mice. Proc Natl Acad Sci U S A. 92 (1995) 4567-4571.
[5] Kaoru Morishita, Daniel E. Johnson, and Lewis T. Williams. A novel promoter for vascular endothelial growth factor receptor (flt-1) that confers endothelial-specific gene expression. J Biol Chem. 270 (1995) 27948-27953.
[6] Gory S, Vernet M, Laurent M, Dejana E, Dalmon J, Huber P. The vascular endothelial-cadherin promoter directs endothelial-specific expression in transgenic mice. Blood 93 (1999) 184-92.
[7] Harats D, Kurihara H, Belloni P, Oakley H, Ziober A, Ackley D, Cain G, Kurihara Y, Lawn R, Sigal E. Targeting gene expression to the vascular wall in transgenic mice using the murine preproendothelin-1 promoter. J Clin Invest. 95 (1995) 1335-44.
[8] Shindo T, Kurihara H, Maemura K, Kurihara Y, Kuwaki T, Izumida T, Minamino N, Ju KH, Morita H, Oh-hashi Y, Kumada M, Kangawa K, Nagai R, Yazaki Y. Hypotension and resistance to lipopolysaccharideinduced shock in transgenic mice overexpressing adrenomedullin in their vasculature. Circulation 101 (2000) 2309-16.
[9] Nicklin SA, Reynolds PN, Brosnan MJ, White SJ, Curiel DT, Dominiczak AF, Baker AH. Analysis of cell-specific promoters for viral gene therapy targeted at the vascular endothelium. Hypertension 38 (2001) 65-70.
[10] Reynolds PN, Nicklin SA, Kaliberova L, Boatman BG, Grizzle WE, Balyasnikova IV, Baker AH, Danilov SM, Curiel DT. Combined transductional and transcriptional targeting improves the specificity of transgene expression in vivo. Nat Biotechnol. 19 (2001) 838-842.
[11] Cowan PJ, Tsang D, Pedic CM, Abbott LR, Shinkel TA, d'Apice AJ, Pearse MJ. The human ICAM-2 promoter is endothelial cell-specific in vitro and in vivo and contains critical Sp1 and GATA binding sites. J Biol Chem. 273 (1998) 11737-11744.
[12] Shinkel TA, Cowan PJ, Barlow H, Aminian A, Romanella M, Lublin DM, Pearse MJ, d'Apice AJ. Expression and functional analysis of glycosyl-phosphatidyl inositol-linked CD46 in transgenic mice. Transplantation 66 (1998) 1401-1406.
[13] Cowan PJ, Shinkel TA, Fisicaro N, Godwin JW, Bernabeu C, Almendro N, Rius C, Lonie AJ, Nottle MB, Wigley PL, Paizis K, Pearse MJ, d'Apice AJ. Targeting gene expression to endothelium in transgenic animals: a comparison of the human ICAM-2, PECAM-1 and endoglin promoters. Xenotransplantation 10 (2003) 223-31.
[14] Jahroudi N, Schmaier A, Srikanth S, Mahdi F, Lutka FA, Bowser R. Von Willebrand factor promoter targets the expression of amyloid beta protein precursor to brain vascular endothelial cells of transgenic mice. J Alzheimers Dis. 5 (2003) 149-58.
[15] Minami T, Donovan DJ, Tsai JC, Rosenberg RD, Aird WC. Differential regulation of the von Willebrand factor and Flt-1 promoters in the endothelium of hypoxanthine phosphoribosyltransferase-targeted mice. Blood 100 (2002) 4019-4025.
[16] Yu SM, Chen CC, Huang YL, Tsai CW, Lin CH, Huang TF, Teng CM. Vasorelaxing effect in rat thoracic aorta caused by denudatin B, isolated from the Chinese herb, magnolia fargesii. Eur J Pharmacol. 187 (1990) 39-47.
[17] Seglen, P. O. Methods Cell Biol. 13 (1976) 29-83.
[18] Ono K, Lindsey ES. Improved technique of heart transplantation in rats. J Thorac Cardiovasc Surg. 57 (1969) 225.