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Cardiovascular Drugs and Therapy

Published in:

01-10-2009

Endothelial Cell Seeding Fails to Prevent Intimal Hyperplasia Following Arterial Injury in the Rat Carotid Model

Authors: Bertram J. Jobst, Guenter A. J. Riegger, Daniel P. Griese

Published in: Cardiovascular Drugs and Therapy | Issue 5/2009

Abstract

Purpose

Aim of the study was to evaluate the therapeutic potential of endothelial cell seeding to inhibit the neointimal response after balloon injury of the rat carotid artery.

Methods and results

Endothelial cells were isolated from peripheral blood after cytokine-stimulation (PB-EC), the bone marrow compartment (BM-EC), and the thoracic aorta (AO-EC) of male rats. The EC-populations were characterized by microscopy, cytofluorometry, and PCR-analysis, and displayed distinct patterns of RNA-expression of the EC-markers VEGF-receptor 1 and 2, and TIE2. 5 × 10⁵ ECs were incubated in the freshly balloon-denuded arterial bed for 30 min achieving about 70% coverage with all 3 EC-populations. However, the neointimal response 2 weeks after the procedure was significantly aggravated in the EC-seeded carotids (I/M-ratio: non-seeded Control 1.00 ± 0.10, PB-EC 1.53 ± 0.07, BM-EC 1.64 ± 0.12, and AO-EC 1.55 ± 0.14; P < 0.05 vs. Control for all). We found evidence for an accelerated cell-turnover (TUNEL-assay, total cell-density, infiltration with CD45^pos haematopoietic cells) especially in the adventitia of the treated vessels.

Conclusion

Endothelial cell seeding fails to prevent intimal hyperplasia following arterial injury in the rat carotid model.

Gibbons GH, Dzau VJ. The emerging concept of vascular remodeling. N Engl J Med. 1994;330(20):1431–1438.CrossRefPubMed

Nikkari ST, Clowes AW. Restenosis after vascular reconstruction. Ann Med. 1994;26:95–100.CrossRefPubMed

Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993;362:801–809.CrossRefPubMed

Rogers C, Welt FG, Karnovsky MJ, Edelman ER. Monocyte recruitment and neointimal hyperplasia in rabbits. Coupled inhibitory effects of heparin. Arterioscler Thromb Vasc Biol. 1996;16:1312–1318.PubMed

Maiellaro K, Taylor WR. The role of the adventitia in vascular inflammation. Cardiovasc Res. 2007;75:640–648.CrossRefPubMed

Fingerle J, Au YP, Clowes AW, Reidy MA. Intimal lesion formation in rat carotid arteries after endothelial denudation in absence of medial injury. Arteriosclerosis. 1990;10:1082–1087.PubMed

Schwartz RS. Pathophysiology of restenosis: interaction of thrombosis, hyperplasia, and/or remodeling. Am J Cardiol. 1998;81:14E–17E.CrossRefPubMed

Rogers C, Parikh S, Seifert P, Edelman ER. Endogenous cell seeding. Remnant endothelium after stenting enhances vascular repair. Circulation. 1996;94:2909–2914.PubMed

Stemerman MB, Spaet TH, Pitlick F, Cintron J, Lejnieks I, Tiell ML. Intimal healing. The pattern of reendothelialization and intimal thickening. Am J Pathol. 1977;87:125–142.PubMed

10.

Walter DH, Rittig K, Bahlmann FH, Kirchmair R, Silver M, Murayama T, et al. Statin therapy accelerates reendothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells. Circulation. 2002;105:3017–3024.CrossRefPubMed

11.

Virmani R, Guagliumi G, Farb A, Musumeci G, Grieco N, Motta T, et al. Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: should we be cautious? Circulation. 2004;109:701–705.CrossRefPubMed

12.

Hack M, Mascha FG, Jobst BJ, Riegger GA, Griese DP. A systemic combination therapy with granulocyte-colony stimulating factor plus erythropoietin aggravates the healing process of balloon- injured rat carotid arteries. Cardiovasc Drugs Ther. 2008;22:351–362.CrossRefPubMed

13.

Haghighat A, Weiss D, Whalin MK, Cowan DP, Taylor WR. Granulocyte colony-stimulating factor and granulocyte macrophage colony-stimulating factor exacerbate atherosclerosis in apolipoprotein E- deficient mice. Circulation. 2007;115:2049–2054.CrossRefPubMed

14.

Aoki J, Serruys PW, van Beusekom H, Ong AT, McFadden EP, Sianos G, et al. Endothelial progenitor cell capture by stents coated with antibody against CD34: the HEALING-FIM (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth-First In Man) Registry. J Am Coll Cardiol. 2005;45:1574–1579.CrossRefPubMed

15.

Melo LG, Gnecchi M, Pachori AS, Kong D, Wang K, Liu X, et al. Endothelium-targeted gene and cell-based therapies for cardiovascular disease. Arterioscler Thromb Vasc Biol. 2004;24:1761–1774.CrossRefPubMed

16.

Kaushal S, Amiel GE, Guleserian KJ, Shapira OM, Perry T, Sutherland FW, et al. Functional small-diameter neovessels created using endothelial progenitor cells expanded ex vivo. Nat Med. 2001;7:1035–1040.CrossRefPubMed

17.

Wilson JM, Birinyi LK, Salomon RN, Libby P, Callow AD, Mulligan RC. Implantation of vascular grafts lined with genetically modified endothelial cells. Science. 1989;244:1344–1346.CrossRefPubMed

18.

Singh P, Williams DJ. Cell therapies: realizing the potential of this new dimension to medical therapeutics. J Tissue Eng Regen Med. 2008;2:307–319.CrossRefPubMed

19.

Griese DP, Ehsan A, Melo LG, Kong D, Zhang L, Mann MJ, et al. Isolation and transplantation of autologous circulating endothelial cells into denuded vessels and prosthetic grafts: implications for cell-based vascular therapy. Circulation. 2003;108:2710–2715.CrossRefPubMed

20.

Gulati R, Jevremovic D, Peterson TE, Witt TA, Kleppe LS, Mueske CS, et al. Autologous culture-modified mononuclear cells confer vascular protection after arterial injury. Circulation. 2003;108:1520–1526.CrossRefPubMed

21.

He T, Smith LA, Harrington S, Nath KA, Caplice NM, Katusic ZS. Transplantation of circulating endothelial progenitor cells restores endothelial function of denuded rabbit carotid arteries. Stroke. 2004;35:2378–2384.CrossRefPubMed

22.

Griese DP, Achatz S, Batzlsperger CA, Strauch UG, Grumbeck B, Weil J, et al. Vascular gene delivery of anticoagulants by transplantation of retrovirally-transduced endothelial progenitor cells. Cardiovasc Res. 2003;58:469–477.CrossRefPubMed

23.

Conte MS, Choudhury RP, Shirakowa M, Fallon JT, Birinyi LK, Choudhry RP. Endothelial cell seeding fails to attenuate intimal thickening in balloon-injured rabbit arteries. J Vasc Surg. 1995;21:413–421.CrossRefPubMed

24.

Conte MS, VanMeter GA, Akst LM, Clemons T, Kashgarian M, Bender JR. Endothelial cell seeding influences lesion development following arterial injury in the cholesterol-fed rabbit. Cardiovasc Res. 2002;53:502–511.CrossRefPubMed

25.

Wang CH, Cherng WJ, Yang NI, Kuo LT, Hsu CM, Yeh HI, et al. Late-outgrowth endothelial cells attenuate intimal hyperplasia contributed by mesenchymal stem cells after vascular injury. Arterioscler Thromb Vasc Biol. 2008;28:54–60.CrossRefPubMed

26.

Schierling W, Kunz-Schughart LA, Muders F, Riegger GA, Griese DP. Fates of genetically engineered haematopoietic and mesenchymal stem cell grafts in normal and injured rat hearts. J Tissue Eng Regen Med. 2008;2:354–364.CrossRefPubMed

27.

Kahler CM, Wechselberger J, Hilbe W, Gschwendtner A, Colleselli D, Niederegger H, et al. Peripheral infusion of rat bone marrow derived endothelial progenitor cells leads to homing in acute lung injury. Respir Res. 2007;8:50.CrossRefPubMed

28.

Batzlsperger CA, Achatz S, Spreng J, Riegger GA, Griese DP. Evidence for a possible inhibitory interaction between the HO-1/CO- and Akt/NO-pathways in human endothelial cells. Cardiovasc Drugs Ther. 2007;21:347–355.CrossRefPubMed

29.

Gulati R, Jevremovic D, Witt TA, Kleppe LS, Vile RG, Lerman A, et al. Modulation of the vascular response to injury by autologous blood-derived outgrowth endothelial cells. Am J Physiol Heart Circ Physiol. 2004;287:H512–517.CrossRefPubMed

30.

Ziegler BL, Valtieri M, Porada GA, De Maria R, Muller R, Masella B, et al. KDR receptor: a key marker defining hematopoietic stem cells. Science. 1999;285:1553–1558.CrossRefPubMed

31.

Yancopoulos GD, Klagsbrun M, Folkman J. Vasculogenesis, angiogenesis, and growth factors: ephrins enter the fray at the border. Cell. 1998;93:661–664.CrossRefPubMed

32.

Shi Y, O’Brien JE, Fard A, Mannion JD, Wang D, Zalewski A. Adventitial myofibroblasts contribute to neointimal formation in injured porcine coronary arteries. Circulation. 1996;94:1655–1664.PubMed

33.

Couffinhal T, Dufourcq P, Jaspard B, Daret D, Allieres C, Alzieu P, et al. Kinetics of adventitial repair in the rat carotid model. Coron Artery Dis. 2001;12:635–648.CrossRefPubMed

34.

Akishita M, Horiuchi M, Yamada H, Zhang L, Shirakami G, Tamura K, et al. Inflammation influences vascular remodeling through AT2 receptor expression and signaling. Physiol Genomics. 2000;2:13–20.PubMed

35.

Arts CH, Hedeman Joosten PP, Blankensteijn JD, Staal FJ, Ng PY, Heijnen-Snyder GJ, et al. Contaminants from the transplant contribute to intimal hyperplasia associated with microvascular endothelial cell seeding. Eur J Vasc Endovasc Surg. 2002;23:29–38.CrossRefPubMed

Title: Endothelial Cell Seeding Fails to Prevent Intimal Hyperplasia Following Arterial Injury in the Rat Carotid Model
Authors: Bertram J. Jobst
Guenter A. J. Riegger
Daniel P. Griese
Publication date: 01-10-2009
Publisher: Springer US
Published in: Cardiovascular Drugs and Therapy / Issue 5/2009
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI: https://doi.org/10.1007/s10557-009-6191-6

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Endothelial Cell Seeding Fails to Prevent Intimal Hyperplasia Following Arterial Injury in the Rat Carotid Model

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Purpose

Methods and results

Conclusion

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