Antisense to Transforming Growth Factor-β1 Facilitates the Apoptosis of Macrophages in Rat Vein GraftsHeaton N.S. · Wolff R.A. · Malinowski R.L. · Hullett D.A. · Hoch J.R.
W.S. Middleton VA Hospital and the University of Wisconsin School of Medicine and Public Health, Madison, Wisc., USA
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Background: The success of peripheral vein grafts is limited by intimal hyperplasia. Transforming growth factor (TGF)-β1 has effects on cell proliferation, apoptosis and extracellular matrix synthesis. We have previously observed positive changes in vessel healing with antisense to TGF-β1. Methods: Adenovirus was used to transduce rat femoral artery vein grafts with antisense to TGF-β1 (Ad-AST) or the sequence encoding the bioactive form of TGF-β1 (Ad-BAT). Grafts were harvested at 1, 2, 4 and 12 weeks and formalin fixed for immunohistochemical studies of the cell markers proliferating cellular nuclear antigen (proliferation) and active caspase 3 (apoptosis). In situ DNA fragmentation assays were also performed to confirm active caspase 3 results. Results: Ad-AST treatment significantly (p = 0.05) increased apoptosis of macrophages inside the internal elastic lamina. In addition, Ad-AST treatment significantly increased the cellularity of the graft at early time points and reduced it at later time points (p = 0.01). Conclusion: The low levels of TGF-β1 in Ad-AST treatment promote apoptosis of macrophages and provide an environment that is more conducive to the proliferation or infiltration of cells that contribute to healthy vessels.
© 2008 S. Karger AG, Basel
- Faries PL, Logerfo FW, Arora S, Hook S, Pulling MC, Akbari CM, Campbell DR, Pomposelli FB Jr: A comparative study of alternative conduits for lower extremity revascularization: all-autogenous conduit versus prosthetic grafts. J Vasc Surg 2000;32:1080–1090.
- Nguyen LL, Conte MS, Menard MT, Gravereaux EC, Chew DK, Donaldson MC, Whittemore AD, Belkin M: Infrainguinal vein bypass graft revision: factors affecting long-term outcome. J Vasc Surg 2004;40:916–923.
- Angelini GD, Jeremy JY: Towards the treatment of saphenous vein bypass graft failure – a perspective of the Bristol Heart Institute. Biorheology 2002;39:491–499.
- Mitra AK, Gangahar DM, Agrawal DK: Cellular, molecular and immunological mechanisms in the pathophysiology of vein graft intimal hyperplasia. Immunol Cell Biol 2006;84:115–124.
- Khan R, Agrotis A, Bobik A: Understanding the role of transforming growth factor-beta1 in intimal thickening after vascular injury. Cardiovasc Res 2007;74:223–234.
- White SJ, Newby AC: Gene therapy for all aspects of vein-graft disease. J Card Surg 2002;17:549–555.
- Grossman M, Raper SE, Kozarsky K, Stein EA, Engelhardt JF, Muller D, Lupien PJ, Wilson JM: Successful ex vivo gene therapy directed to liver in a patient with familial hypercholesterolaemia. Nat Genet 1994;6:335–341.
- Friedl R, Li J, Schumacher B, Hanke H, Waltenberger J, Hannekum A, Stracke S: Intimal hyperplasia and expression of transforming growth factor-beta1 in saphenous veins and internal mammary arteries before coronary artery surgery. Ann Thorac Surg 2004;78:1312–1318.
- Ignotz RA, Massague J: Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem 1986;261:4337–4345.
- Cipollone F, Fazia M, Mincione G, Iezzi A, Pini B, Cuccurullo C, Ucchino S, Spigonardo F, Di Nisio M, Cuccurullo F, Mezzetti A, Porreca E: Increased expression of transforming growth factor-beta 1 as a stabilizing factor in human atherosclerotic plaques. Stroke 2004;35:2253–2257.
- Ward MR, Agrotis A, Kanellakis P, Hall J, Jennings G, Bobik A: Tranilast prevents activation of transforming growth factor-beta system, leukocyte accumulation, and neointimal growth in porcine coronary arteries after stenting. Arterioscler Thromb Vasc Biol 2002;22:940–948.
- Singh NN, Ramji DP: The role of transforming growth factor-beta in atherosclerosis. Cytokine Growth Factor Rev 2006;17:487–499.
- Chin BY, Petrache I, Choi AM, Choi ME: Transforming growth factor beta1 rescues serum deprivation-induced apoptosis via the mitogen-activated protein kinase (MAPK) pathway in macrophages. J Biol Chem 1999;274:11362–11368.
- Furukawa Y, Matsumori A, Ohashi N, Shioi T, Ono K, Harada A, Matsushima K, Sasayama S: Anti-monocyte chemoattractant protein-1/monocyte chemotactic and activating factor antibody inhibits neointimal hyperplasia in injured rat carotid arteries. Circ Res 1999;84:306–314.
- Wahl SM, Hunt DA, Wakefield LM, Cartney-Francis N, Wahl LM, Roberts AB, Sporn MB: Transforming growth factor type beta induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sci USA 1987;84:5788–5792.
- Owens GK, Kumar MS, Wamhoff BR: Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev 2004;84:767–801.
- Desmouliere A, Chaponnier C, Gabbiani G: Tissue repair, contraction, and the myofibroblast. Wound Repair Regen 2005;13:7–12.
- Fukui D, Miyagawa S, Soeda J, Tanaka K, Urayama H, Kawasaki S: Overexpression of transforming growth factor beta1 in smooth muscle cells of human abdominal aortic aneurysm. Eur J Vasc Endovasc Surg 2003;25:540–545.
- Hyman KM, Seghezzi G, Pintucci G, Stellari G, Kim JH, Grossi EA, Galloway AC, Mignatti P: Transforming growth factor-beta1 induces apoptosis in vascular endothelial cells by activation of mitogen-activated protein kinase. Surgery 2002;132:173–179.
- Hoch JR, Stark VK, Turnipseed WD: The temporal relationship between the development of vein graft intimal hyperplasia and growth factor gene expression. J Vasc Surg 1995;22:51–58.
- Wolff RA, Ryomoto M, Stark VE, Malinowski R, Tomas JJ, Stinauer MA, Hullett DA, Hoch JR: Antisense to transforming growth factor-beta1 messenger RNA reduces vein graft intimal hyperplasia and monocyte chemotactic protein 1. J Vasc Surg 2005;41:498–508.
- Wolff RA, Malinowski RL, Heaton NS, Hullett DA, Hoch JR: Transforming growth factor-beta1 antisense treatment of rat vein grafts reduces the accumulation of collagen and increases the accumulation of h-caldesmon. J Vasc Surg 2006;43:1028–1036.
- Brunner AM, Marquardt H, Malacko AR, Lioubin MN, Purchio AF: Site-directed mutagenesis of cysteine residues in the pro region of the transforming growth factor beta 1 precursor. Expression and characterization of mutant proteins. J Biol Chem 1989;264:13660–13664.
- Wolf BB, Schuler M, Echeverri F, Green DR: Caspase-3 is the primary activator of apoptotic DNA fragmentation via DNA fragmentation factor-45/inhibitor of caspase-activated DNase inactivation. J Biol Chem 1999;274:30651–30656.
- Ceballos KM, Nielsen GP, Selig MK, O’Connell JX: Is anti-h-caldesmon useful for distinguishing smooth muscle and myofibroblastic tumors? An immunohistochemical study. Am J Clin Pathol 2000;114:746–753.
- Watanabe K, Tajino T, Sekiguchi M, Suzuki T: h-Caldesmon as a specific marker for smooth muscle tumors – comparison with other smooth muscle markers in bone tumors. Am J Clin Pathol 2000;113:663–668.
- Bujak M, Frangogiannis NG: The role of TGF-beta signaling in myocardial infarction and cardiac remodeling. Cardiovasc Res 2007;74:184–195.
- Leask A, Abraham DJ: TGF-beta signaling and the fibrotic response. FASEB J 2004;18:816–827.
- McKarns SC, Letterio JJ, Kaminski NE: Concentration-dependent bifunctional effect of TGF-beta 1 on immunoglobulin production: a role for Smad3 in IgA production in vitro. Int Immunopharmacol 2003;3:1761–1774.
- Pollman MJ, Naumovski L, Gibbons GH: Vascular cell apoptosis: cell type-specific modulation by transforming growth factor-beta1 in endothelial cells versus smooth muscle cells. Circulation 1999;99:2019–2026.
- Zhang HY, Phan SH: Inhibition of myofibroblast apoptosis by transforming growth factor beta(1). Am J Respir Cell Mol Biol 1999;21:658–665.
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