Background/Aims: Arteries and veins modulate cardiovascular homeostasis and contribute to hypertension pathogenesis. Functional differences between arteries and veins are based upon differences in gene expression. To better characterize these expression patterns, and to identify candidate genes that could be manipulated selectively in the venous system, we performed whole genome expression profiling of arteries and veins. Methods: We used the CodeLink platform and the major artery (thoracic aorta) and vein (caudal vena cava) of the rat. Results: The most prominent difference was pancreatitis-associated protein (PAP1), expressed 64-fold higher in vena cava versus aorta. Expression of mRNA for thrombospondins (TSP-1, TSP-4) was greater than 5-fold higher in veins versus arteries. Higher mRNA expression of TSP-1, TSP-2, TSP-4 and PAP1 in vena cava versus aorta was confirmed by PCR. Immunohistochemical analysis of tissue sections qualitatively confirmed a higher expression of these proteins in vena cava versus aorta. Conclusion: This is the first gene array study of adult rat arterial and venous tissues, and also the first study to report differences in inflammatory genes between arteries and veins. Data from these studies may provide novel insights into the genetic basis for functional differences between arteries and veins in health and disease.

1.
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003;289:2560–2572.
2.
Martin DS, Rodrigo MC, Appelt CW: Venous tone in the developmental stages of spontaneous hypertension. Hypertension 1998;31:139–144.
3.
Pan YJ, Young DB: Experimental aldosterone hypertension in the dog. Hypertension 1982;4:279–287.
4.
Yamamoto J, Trippodo NC, MacPhee AA, Frohlich ED: Decreased total venous capacity in Goldblatt hypertensive rats. Am J Physiol 1981;240:H487–H492.
5.
Ricksten SE, Yao T, Thoren P: Peripheral and central vascular compliances in conscious normotensive and spontaneously hypertensive rats. Acta Physiol Scand 1981;112:169–177.
6.
Safar ME, London GM: Arterial and venous compliance in sustained essential hypertension. Hypertension 1987;10:133–139.
7.
Nyhof RA, Laine GA, Meininger GA, Granger HJ: Splanchnic circulation in hypertension. Fed Proc 1983;42:1690–1693.
8.
London GM, Safar ME, Weiss YA, Simon CA: Total effective compliance of the vascular bed in essential hypertension. Am Heart J 1978;95:325–330.
9.
Schmieder RE, Schobel HP, Messerli FH: Central blood volume: a determinant of early cardiac adaptation in arterial hypertension? J Am Coll Cardiol 1995;26:1692–1698.
10.
Swales JD: Textbook of Hypertension. Oxford, Blackwell Scientific Publications, 1994.
11.
Adams RH: Molecular control of arterial-venous blood vessel identity. J Anat 2003;202:105–112.
12.
Egea J, Klein R: Bidirectional Eph-ephrin signaling during axon guidance. Trends Cell Biol 2007;17:230–238.
13.
Eichmann A, Yuan L, Moyon D, Lenoble F, Pardanaud L, Breant C: Vascular development: from precursor cells to branched arterial and venous networks. Int J Dev Biol 2005;49:259–267.
14.
Harvey NL, Oliver G: Choose your fate: artery, vein or lymphatic vessel? Curr Opin Genet Dev 2004;14:499–505.
15.
Hofmann JJ, Iruela-Arispe ML: Notch signaling in blood vessels: who is talking to whom about what? Circ Res 2007;100:1556–1568.
16.
Kuijper S, Turner CJ, Adams RH: Regulation of angiogenesis by Eph-ephrin interactions. Trends Cardiovasc Med 2007;17:145–151.
17.
Lanner F, Sohl M, Farnebo F: Functional arterial and venous fate is determined by graded VEGF signaling and notch status during embryonic stem cell differentiation. Arterioscler Thromb Vasc Biol 2007;27:487–493.
18.
Lawson ND, Scheer N, Pham VN, Kim CH, Chitnis AB, Campos-Ortega JA, Weinstein BM: Notch signaling is required for arterial-venous differentiation during embryonic vascular development. Development 2001;128:3675–3683.
19.
Yamashita JK: Differentiation of arterial, venous, and lymphatic endothelial cells from vascular progenitors. Trends Cardiovasc Med 2007;17:59–63.
20.
Rozen S, Skaletsky H: Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 2000;132:365–386.
21.
Edgar R, Domrachev M, Lash AE: Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res 2002;30:207–210.
22.
Katsumata N, Chakraborty C, Myal Y, Schroedter IC, Murphy LJ, Shiu RP, Friesen HG: Molecular cloning and expression of peptide 23, a growth hormone-releasing hormone-inducible pituitary protein. Endocrinology 1995;136:1332–1339.
23.
Closa D, Motoo Y, Iovanna JL: Pancreatitis-associated protein: from a lectin to an anti-inflammatory cytokine. World J Gastroenterol 2007;13:170–174.
24.
Folch-Puy E, Granell S, Dagorn JC, Iovanna JL, Closa D: Pancreatitis-associated protein I suppresses NF-κB activation through a JAK/STAT-mediated mechanism in epithelial cells. J Immunol 2006;176:3774–3779.
25.
Lin YY, Viterbo D, Mueller CM, Stanek AE, Smith-Norowitz T, Drew H, Wadgaonkar R, Zenilman ME, Bluth MH: Small-interference RNA gene knockdown of pancreatitis-associated proteins in rat acute pancreatitis. Pancreas 2008;36:402–410.
26.
Ortiz EM, Dusetti NJ, Vasseur S, Malka D, Bodeker H, Dagorn JC, Iovanna JL: The pancreatitis-associated protein is induced by free radicals in AR4-2J cells and confers cell resistance to apoptosis. Gastroenterology 1998;114:808–816.
27.
Adams JC, Lawler J: The thrombospondins. Int J Biochem Cell Biol 2004;36:961–968.
28.
Lee NV, Sato M, Annis DS, Loo JA, Wu L, Mosher DF, Iruela-Arispe ML: ADAMTS1 mediates the release of antiangiogenic polypeptides from TSP1 and 2. EMBO J 2006;25:5270–5283.
29.
Good DJ, Polverini PJ, Rastinejad F, Le Beau MM, Lemons RS, Frazier WA, Bouck NP: A tumor suppressor-dependent inhibitor of angiogenesis is immunologically and functionally indistinguishable from a fragment of thrombospondin. Proc Natl Acad Sci USA 1990;87:6624–6628.
30.
Chatila K, Ren G, Xia Y, Huebener P, Bujak M, Frangogiannis NG: The role of the thrombospondins in healing myocardial infarcts. Cardiovasc Hematol Agents Med Chem 2007;5:21–27.
31.
Daniel C, Amann K, Hohenstein B, Bornstein P, Hugo C: Thrombospondin 2 functions as an endogenous regulator of angiogenesis and inflammation in experimental glomerulonephritis in mice. J Am Soc Nephrol 2007;18:788–798.
32.
Hogg PJ, Owensby DA, Mosher DF, Misenheimer TM, Chesterman CN: Thrombospondin is a tight-binding competitive inhibitor of neutrophil elastase. J Biol Chem 1993;268:7139–7146.
33.
Kuznetsova SA, Issa P, Perruccio EM, Zeng B, Sipes JM, Ward Y, Seyfried NT, Fielder HL, Day AJ, Wight TN, Roberts DD: Versican-thrombospondin-1 binding in vitro and colocalization in microfibrils induced by inflammation on vascular smooth muscle cells. J Cell Sci 2006;119:4499–4509.
34.
Lamy L, Foussat A, Brown EJ, Bornstein P, Ticchioni M, Bernard A: Interactions between CD47 and thrombospondin reduce inflammation. J Immunol 2007;178:5930–5939.
35.
Lawler J: Thrombospondin-1 as an endogenous inhibitor of angiogenesis and tumor growth. J Cell Mol Med 2002;6:1–12.
36.
Lawler J, Detmar M: Tumor progression: the effects of thrombospondin-1 and -2. Int J Biochem Cell Biol 2004;36:1038–1045.
37.
Park YW, Kang YM, Butterfield J, Detmar M, Goronzy JJ, Weyand CM: Thrombospondin 2 functions as an endogenous regulator of angiogenesis and inflammation in rheumatoid arthritis. Am J Pathol 2004;165:2087–2098.
38.
Adams LD, Geary RL, McManus B, Schwartz SM: A comparison of aorta and vena cava medial message expression by cDNA array analysis identifies a set of 68 consistently differentially expressed genes, all in aortic media. Circ Res 2000;87:623–631.
39.
Shin D, Anderson DJ: Isolation of arterial-specific genes by subtractive hybridization reveals molecular heterogeneity among arterial endothelial cells. Dev Dyn 2005;233:1589–1604.
40.
Deng DX, Spin JM, Tsalenko A, Vailaya A, Ben-Dor A, Yakhini Z, Tsao P, Bruhn L, Quertermous T: Molecular signatures determining coronary artery and saphenous vein smooth muscle cell phenotypes: distinct responses to stimuli. Arterioscler Thromb Vasc Biol 2006;26:1058–1065.
41.
Deng DX, Tsalenko A, Vailaya A, Ben-Dor A, Kundu R, Estay I, Tabibiazar R, Kincaid R, Yakhini Z, Bruhn L, Quertermous T: Differences in vascular bed disease susceptibility reflect differences in gene expression response to atherogenic stimuli. Circ Res 2006;98:200–208.
42.
Payeli SK, Latini R, Gebhard C, Patrignani A, Wagner U, Luscher TF, Tanner FC: Prothrombotic gene expression profile in vascular smooth muscle cells of human saphenous vein, but not internal mammary artery. Arterioscler Thromb Vasc Biol 2008;28:705–710.
43.
Mecha Disassa N, Styp-Rekowska B, Hinz B, Da Silva-Azevedo L, Pries AR, Zakrzewicz A: Differential expression of VEGFA, TIE2, and ANG2 but not ADAMTS1 in rat mesenteric microvascular arteries and veins. Physiol Res 2008, Epub ahead of print.
44.
Callera GE, Montezano AC, Touyz RM, Zorn TM, Carvalho MH, Fortes ZB, Nigro D, Schiffrin EL, Tostes RC: ETA receptor mediates altered leukocyte-endothelial cell interaction and adhesion molecules expression in DOCA-salt rats. Hypertension 2004;43:872–879.
45.
Guzik TJ, Mangalat D, Korbut R: Adipocytokines – novel link between inflammation and vascular function? J Physiol Pharmacol 2006;57:505–528.
46.
Henke N, Schmidt-Ullrich R, Dechend R, Park JK, Qadri F, Wellner M, Obst M, Gross V, Dietz R, Luft FC, Scheidereit C, Muller DN: Vascular endothelial cell-specific NF-κB suppression attenuates hypertension-induced renal damage. Circ Res 2007;101:268–276.
47.
Horstman LL, Jy W, Jimenez JJ, Ahn YS: Endothelial microparticles as markers of endothelial dysfunction. Front Biosci 2004;9:1118–1135.
48.
Kalogeris TJ, Kevil CG, Laroux FS, Coe LL, Phifer TJ, Alexander JS: Differential monocyte adhesion and adhesion molecule expression in venous and arterial endothelial cells. Am J Physiol 1999;276:L9–L19.
49.
Ley K, Gaehtgens P: Endothelial, not hemodynamic, differences are responsible for preferential leukocyte rolling in rat mesenteric venules. Circ Res 1991;69:1034–1041.
50.
Kevil CG, Okayama N, Trocha SD, Kalogeris TJ, Coe LL, Specian RD, Davis CP, Alexander JS: Expression of zonula occludens and adherens junctional proteins in human venous and arterial endothelial cells: role of occludin in endothelial solute barriers. Microcirculation 1998;5:197–210.
51.
Watts SW, Rondelli C, Thakali K, Li X, Uhal B, Pervaiz MH, Watson RE, Fink GD: Morphological and biochemical characterization of remodeling in aorta and vena cava of DOCA-salt hypertensive rats. Am J Physiol Heart Circ Physiol 2007;292:H2438–H2448.
52.
Deatrick KB, Eliason JL, Lynch EM, Moore AJ, Dewyer NA, Varma MR, Pearce CG, Upchurch GR, Wakefield TW, Henke PK: Vein wall remodeling after deep vein thrombosis involves matrix metalloproteinases and late fibrosis in a mouse model. J Vasc Surg 2005;42:140–148.
53.
Gusic RJ, Myung R, Petko M, Gaynor JW, Gooch KJ: Shear stress and pressure modulate saphenous vein remodeling ex vivo. J Biomech 2005;38:1760–1769.
54.
Pascarella L, Penn A, Schmid-Schonbein GW: Venous hypertension and the inflammatory cascade: major manifestations and trigger mechanisms. Angiology 2005;56 (suppl 1):S3–S10.
55.
Pascarella L, Schmid-Schonbein GW, Bergan J: An animal model of venous hypertension: the role of inflammation in venous valve failure. J Vasc Surg 2005;41:303–311.
56.
Takase S, Pascarella L, Bergan JJ, Schmid-Schonbein GW: Hypertension-induced venous valve remodeling. J Vasc Surg 2004;39:1329–1334.
57.
Henke PK, Varma MR, Deatrick KB, Dewyer NA, Lynch EM, Moore AJ, Dubay DA, Sukheepod P, Pearce CG, Upchurch GR Jr, Kunkel SL, Franz MG, Wakefield TW: Neutrophils modulate post-thrombotic vein wall remodeling but not thrombus neovascularization. Thromb Haemost 2006;95:272–281.
58.
Schachner T: Pharmacologic inhibition of vein graft neointimal hyperplasia. J Thorac Cardiovasc Surg 2006;131:1065–1072.
59.
Schachner T, Laufer G, Bonatti J: In vivo (animal) models of vein graft disease. Eur J Cardiothorac Surg 2006;30:451–463.
60.
Scatena M, Liaw L, Giachelli CM: Osteopontin: a multifunctional molecule regulating chronic inflammation and vascular disease. Arterioscler Thromb Vasc Biol 2007;27:2302–2309.
61.
Sorescu GP, Sykes M, Weiss D, Platt MO, Saha A, Hwang J, Boyd N, Boo YC, Vega JD, Taylor WR, Jo H: Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress stimulates an inflammatory response. J Biol Chem 2003;278:31128–31135.
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