Origin of Neointimal Cells in Autologous Vein Graft
2004; Lippincott Williams & Wilkins; Volume: 24; Issue: 7 Linguagem: Inglês
10.1161/01.atv.0000134296.22448.eb
ISSN1524-4636
Autores Tópico(s)Coronary Interventions and Diagnostics
ResumoHomeArteriosclerosis, Thrombosis, and Vascular BiologyVol. 24, No. 7Origin of Neointimal Cells in Autologous Vein Graft Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBOrigin of Neointimal Cells in Autologous Vein Graft Masataka Sata and Ryozo Nagai Masataka SataMasataka Sata From the Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine, Tokyo, Japan. and Ryozo NagaiRyozo Nagai From the Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine, Tokyo, Japan. Originally published1 Jul 2004https://doi.org/10.1161/01.ATV.0000134296.22448.ebArteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1147–1149Since the first aortocoronary vein graft implantation was performed in 1967,1 vascular bypass surgery using saphenous vein grafts has become an established therapeutic procedure for patients with ischemic coronary or peripheral arterial diseases. Despite increasing use of arterial grafts in coronary bypass surgery,2 autologous vein remains an important and convenient conduit for surgical revascularization.3 However, vein grafts are associated with poor long-term patencies.4 During the first year after bypass surgery, up to 15% of venous grafts occlude. Between 1 and 6 years, the graft attrition rate is 1% to 2% per year, which increases to 4% between 6 and 10 years after surgery.5 By 10 years, only 60% of vein grafts are patent and only 50% of patent vein grafts are free of significant stenosis.5See page 1180Graft occlusion arises either from early thrombosis or from the later onset of graft narrowing.3 After implantation, the vein graft is exposed to immediate increases in flow, shear stress, circumferential stress, radial deformation, and pulsatile stress.6 Progressive thickening of vein grafts, mainly caused by neointima formation in the inner layer, is supposed to be the adaptation of these vessels from the low-pressure venous system to the arterial circulation. Smooth muscle cell (SMC) accumulation7,8 and matrix biosynthesis by SMCs4,9 are key events in the pathogenesis of neointima formation in vein grafts. However, the molecular mechanism of SMC hyperplasia is largely unknown. Consequently, no effective therapy has been established to prevent vein graft failure.Experimental models of venous bypass graft have been described in dogs,6 rabbits,10 and rats.11 Recent advance in gene-manipulating techniques enables us to produce various genetically modified mice to determine the role of specific molecules in a variety of biological phenomena including vascular remodeling.12–14 Moreover, genetically modified mice harboring marker genes have become available to identify the origin of the cells that contribute to organ remodeling.15–17 Thus, mouse models of vein graft would greatly facilitate genetic analyses of the pathogenesis of neointimal formation. Recent reports described murine models of vein grafts that produced progressive vessel narrowing caused by SMC hyperplasia.18–20The first evidence for the origin of neointimal cells was provided by Hu et al, who isografted vena cava segment from wild-type mouse to the carotid artery of another mouse that expressed a marker gene, LacZ, in all tissues (ROSA26 mouse).19,21 The authors found that ≈40% of SMCs originated from the recipient and 60% from the donor vessel.19 The same group also reported that a large number of endothelial cells in vein grafts underwent apoptosis or necrosis during the first few days and that circulating recipient cells regenerate the endothelium.21 Because it is crucial to identify the exact source of neointimal cells for the development of genetic or pharmacological strategies to prevent vein graft disease,22 the main findings by Hu et al remain to be confirmed by other laboratories.In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Cooley describes a new mouse model of vein graft transplantation.23 The author interpositioned a smaller-diameter graft, a branch of the jugular vein, to the femoral artery. This model has clinical analogy in terms of graft-to-artery diameter match. The grafts were placed into a similar anatomic location as in clinical femoral–popliteal bypass grafting using end-to-end microvascular anastomoses. Compared with other vein graft models of larger species6,10,11 and mice,18,20 the relative neointimal wall thickness was much greater in Cooley's model, even showing near-occlusive stenosis of the perianastomotic region. However, there was no neointimal formation throughout the arterial graft. Therefore, this graft model seems to be more analogous to human aortocoronary bypass surgery than others. Taking advantage of this model, Cooley investigated the origin of neointimal cells and endothelial cells in vein graft stenotic lesions.23 In contrast to the initial reports by Hu et al,18,19,21 Cooley found that donor-originating cells made a major contribution to neointimal formation. Moreover, the donor-derived endothelial cells also survived and maintained endothelium on the luminal side of the stenotic lesion (Table). Differences Between 2 Mouse Models of Vein GraftHu et al Model18,19,21Cooley Model23Method Vein graft (donor)Vena cava (10-mm length, isogeneic)A branch of the jugular vein (2-mm length, isogeneic) Grafted artery (recipient)Carotid arteryFemoral artery Mode of anastomosisEnd-to-end anastomosisEnd-to-end anastomosis Method of anastomosisSleeving over the cuffsInterrupted stitches of nylon suture Graft-to-artery diameter matchGraft is much larger than arteryClinically analogousResults Origin of endotheliumRecipient-derived endothelial progenitor cellsDonor-derived cells Origin of neointimal cells40% of recipient-derived cellsDonor-derived cells60% of donor-derived cellsThese opposite results apparently result from different experimental systems to test the hypothesis (Figure). In Hu et al's model,18,19,21 isogeneic vena cava vein was grafted between the 2 ends of the carotid artery by sleeving the ends of the vein over the cuffs, over which the carotid arterial ends were turned inside-out. In contrast, Cooley interpositioned a smaller-diameter graft to the femoral artery, using 6 to 10 interrupted stitches of nylon suture per end-to-end anastomosis.23 It is plausible that those differences in surgical procedures significantly influenced the cellular composition of the neointima and endothelium, although both models showed similar neointimal hyperplasia throughout the vein grafts. Consistent with this notion, it was reported that the origin of neointimal cells in transplant-associated arteriosclerosis differed among different allograft models.17,24,25 Moreover, we reported that recruitment of bone marrow-derived cells to vascular lesions depends largely on the type of vascular injury.26–28Download figureDownload PowerPointContrasting results from different murine models of vein graft. A, Hu et al18,19,21 isografted the vena cava segment from wild-type mouse to the carotid artery of ROSA26 mouse by sleeving the ends of the vein over the cuffs placed at the ends of the carotid artery. In this model, ≈40% of SMCs originated from the recipient (shown in blue) and 60% from the donor vessel (shown in red). Recipient cells also contributed to regeneration of the endothelium. B, Cooley23 interpositioned a smaller-diameter venous graft to the femoral artery of ROSA 26 mouse using end-to-end microvascular anastomoses. Neointima and endothelium were exclusively composed of donor-originating cells (shown in red).Given the complexity of human vascular lesions, no animal model would represent exact pathophysiology of human autologous vein graft disease. There are many inherent differences between animals and humans in physiological and pathological responses to mechanical and humoral stimuli. For instance, experimental vein grafts show a characteristic burst of neointimal cell proliferation early after grafting, which leads to a thickened intimal layer by 1 month. This neointimal growth appears to be stabilized beyond 1 to 2 months in most of the animal models,29,30 thus differing from the clinical progression of vein graft narrowing.5 We suggest caution before extrapolating results obtained from an animal model to the pathogenesis of human vein graft stenosis. For better understanding of vein graft disease, we should compare molecular processes of neointima hyperplasia in different models with regard to clinical analogy.FootnotesCorrespondence to Dr Masataka Sata, Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine, 7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655 Japan. E-mail [email protected] References 1 Garrett HE, Dennis EW, DeBakey ME. Aortocoronary bypass with saphenous vein graft. Seven-year follow-up. JAMA. 1973; 223: 792–794.CrossrefMedlineGoogle Scholar2 Tatoulis J, Buxton BF, Fuller JA. Patencies of 2127 arterial to coronary conduits over 15 years. Ann Thorac Surg. 2004; 77: 93–101.CrossrefMedlineGoogle Scholar3 Mehta D, Izzat MB, Bryan AJ, Angelini GD. Towards the prevention of vein graft failure. Int J Cardiol. 1997; 62: S55–S63.CrossrefMedlineGoogle Scholar4 Gentile AT, Mills JL, Westerband A, Gooden MA, Berman SS, Boswell CA, Williams SK. Characterization of cellular density and determination of neointimal extracellular matrix constituents in human lower extremity vein graft stenoses. Cardiovasc Surg. 1999; 7: 464–469.CrossrefMedlineGoogle Scholar5 Motwani JG, Topol EJ. Aortocoronary saphenous vein graft disease: pathogenesis, predisposition, and prevention. Circulation. 1998; 97: 916–931.CrossrefMedlineGoogle Scholar6 Dobrin PB, Littooy FN, Endean ED. Mechanical factors predisposing to intimal hyperplasia and medial thickening in autogenous vein grafts. Surgery. 1989; 105: 393–400.MedlineGoogle Scholar7 Ross R. Atherosclerosis-An inflammatory disease. N Engl J Med. 1999; 340: 115–126.CrossrefMedlineGoogle Scholar8 Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993; 362: 801–809.CrossrefMedlineGoogle Scholar9 Westerband A, Mills JL, Marek JM, Heimark RL, Hunter GC, Williams SK. Immunocytochemical determination of cell type and proliferation rate in human vein graft stenoses. J Vasc Surg. 1997; 25: 64–73.CrossrefMedlineGoogle Scholar10 Leville CD, Osipov VO, Jean-Claude JM, Seabrook GR, Towne JB, Cambria RA. All-trans-retinoic acid decreases cell proliferation and increases apoptosis in an animal model of vein bypass grafting. Surgery. 2000; 128: 178–184.CrossrefMedlineGoogle Scholar11 Dilley RJ, McGeachie JK, Tennant M. The role of cell proliferation and migration in the development of a neo-intimal layer in veins grafted into arteries, in rats. Cell Tissue Res. 1992; 269: 281–287.CrossrefMedlineGoogle Scholar12 Sata M, Tanaka K, Ishizaka N, Hirata Y, Nagai R. Absence of p53 Leads to Accelerated Neointimal Hyperplasia After Vascular Injury. Arterioscler Thromb Vasc Biol. 2003; 23: 1548–1552.LinkGoogle Scholar13 Sata M, Sugiura S, Yoshizumi M, Ouchi Y, Hirata Y, Nagai R. Acute and chronic smooth muscle cell apoptosis after mechanical vascular injury can occur independently of the Fas-death pathway. Arterioscler Thromb Vasc Biol. 2001; 21: 1733–1737.CrossrefMedlineGoogle Scholar14 Sata M, Takahashi A, Tanaka K, Washida M, Ishizaka N, Ako J, Yoshizumi M, Ouchi Y, Taniguchi T, Hirata Y, Yokoyama M, Nagai R, Walsh K. Mouse genetic evidence that tranilast reduces smooth muscle cell hyperplasia via a p21(WAF1)-dependent pathway. Arterioscler Thromb Vasc Biol. 2002; 22: 1305–1309.LinkGoogle Scholar15 Saiura A, Sata M, Washida M, Sugawara Y, Hirata Y, Nagai R, Makuuchi M. Little evidence for cell fusion between recipient and Donor-Derived cells. J Surg Res. 2003; 113: 222–227.CrossrefMedlineGoogle Scholar16 Saiura A, Sata M, Hirata Y, Nagai R, Makuuchi M. Circulating smooth muscle progenitor cells contribute to atherosclerosis. Nat Med. 2001; 7: 382–383.CrossrefMedlineGoogle Scholar17 Sata M, Saiura A, Kunisato A, Tojo A, Okada S, Tokuhisa T, Hirai H, Makuuchi M, Hirata Y, Nagai R. Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis. Nat Med. 2002; 8: 403–409.CrossrefMedlineGoogle Scholar18 Zou Y, Dietrich H, Hu Y, Metzler B, Wick G, Xu Q. Mouse model of venous bypass graft arteriosclerosis. Am J Pathol. 1998; 153: 1301–1310.CrossrefMedlineGoogle Scholar19 Hu Y, Mayr M, Metzler B, Erdel M, Davison F, Xu Q. Both donor and recipient origins of smooth muscle cells in vein graft atherosclerotic lesions. Circ Res. 2002; 91: e13–e20.LinkGoogle Scholar20 Zhang L, Hagen PO, Kisslo J, Peppel K, Freedman NJ. Neointimal hyperplasia rapidly reaches steady state in a novel murine vein graft model. J Vasc Surg. 2002; 36: 824–832.CrossrefMedlineGoogle Scholar21 Xu Q, Zhang Z, Davison F, Hu Y. Circulating progenitor cells regenerate endothelium of vein graft atherosclerosis, which is diminished in ApoE-deficient mice. Circ Res. 2003; 93: e76–e86.LinkGoogle Scholar22 Mann MJ, Dzau VJ. Therapeutic applications of transcription factor decoy oligonucleotides. J Clin Invest. 2000; 106: 1071–1075.CrossrefMedlineGoogle Scholar23 Cooley BC. A murine model of neointimal formation and stenosis in vein grafts. Arterioscler Thromb Vasc Biol. 2004; 24: 1180–1185.LinkGoogle Scholar24 Shimizu K, Sugiyama S, Aikawa M, Fukumoto Y, Rabkin E, Libby P, Mitchell RN. Host bone-marrow cells are a source of donor intimal smooth- muscle-like cells in murine aortic transplant arteriopathy. Nat Med. 2001; 7: 738–741.CrossrefMedlineGoogle Scholar25 Hu Y, Davison F, Ludewig B, Erdel M, Mayr M, Url M, Dietrich H, Xu Q. Smooth muscle cells in transplant atherosclerotic lesions are originated from recipients, but not bone marrow progenitor cells. Circulation. 2002; 106: 1834–1839.LinkGoogle Scholar26 Li S, Fan YS, Chow LH, Van Den Diepstraten C, van Der Veer E, Sims SM, Pickering JG. 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Surgery. 1994; 116: 463–470.MedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Chen D, Zhang C, Chen J, Yang M, Afzal T, An W, Maguire E, He S, Luo J, Wang X, Zhao Y, Wu Q and Xiao Q (2020) miRNA ‐200c‐ 3p promotes endothelial to mesenchymal transition and neointimal hyperplasia in artery bypass grafts , The Journal of Pathology, 10.1002/path.5574, 253:2, (209-224), Online publication date: 1-Feb-2021. Fu C, Yu P, Tao M, Gupta T, Moldawer L, Berceli S and Jiang Z (2012) Monocyte Chemoattractant Protein-1/CCR2 Axis Promotes Vein Graft Neointimal Hyperplasia Through Its Signaling in Graft-Extrinsic Cell Populations, Arteriosclerosis, Thrombosis, and Vascular Biology, 32:10, (2418-2426), Online publication date: 1-Oct-2012. Cooley B (2007) Mouse Strain Differential Neointimal Response in Vein Grafts and Wire-Injured Arteries, Circulation Journal, 10.1253/circj.71.1649, 71:10, (1649-1652), . Xu Q (2004) Mouse Models of Vein Grafts, Arteriosclerosis, Thrombosis, and Vascular Biology, 24:11, (e185-e187), Online publication date: 1-Nov-2004. Tseng C, Karlöf E, Chang Y, Lengquist M, Rotzius P, Berggren P, Hedin U, Eriksson E and Sperandio M (2014) Contribution of Endothelial Injury and Inflammation in Early Phase to Vein Graft Failure: The Causal Factors Impact on the Development of Intimal Hyperplasia in Murine Models, PLoS ONE, 10.1371/journal.pone.0098904, 9:6, (e98904) July 2004Vol 24, Issue 7 Advertisement Article InformationMetrics https://doi.org/10.1161/01.ATV.0000134296.22448.ebPMID: 15237090 Originally publishedJuly 1, 2004 PDF download Advertisement
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