To assess the effect of intensive statins therapy on the outcome of small-diameter vascular prosthesis, we investigated whether atorvastatin treatment (30 mg/d) could accelerate the re-endothelialization process and improve the patency rate in a canine infrarenal abdominal aorta-expanded polytetrafluoroethylene (ePTFE) bypass model. Furthermore, we also evaluated the effect of atorvastatin on the migratory and adherent capacity of circulating endothelial progenitor cells (EPCs) in vitro. Improved patency was confirmed by Doppler sonography and arteriography. Histological and scanning electron microscopy illustrated enhanced re-endothelialization process. Treatment with atorvastatin enhanced the circulating pool of EPCs with fortified migratory and adherent capacity. Reverse transcriptase—polymerase chain reaction (RT-PCR) analysis showed that atorvastatin treatment increased endothelial nitric oxide synthase (eNOS) and kinase insert domain receptor (KDR) messenger RNA (mRNA) expression in cultured EPCs and neointima. In conclusion, intensive statin therapy could be considered a favorable option to improve small-diameter vascular graft patency.
Klinkert P., Schepers A., Burger DH, van Bockel JH, Breslau PJVein versus polytetrafluoroethylene in above-knee femoropopliteal bypass grafting: five-year results of a randomized controlled trial. J Vasc Surg. 2003;37(1):149-155.
2.
Bordenave L. , Menu P., Baquey C.Developments towards tissue-engineered, small-diameter arterial substitutes. Expert Rev Med Devices. 2008;5(3):337-347.
3.
Sayers RD, Raptis S., Berce M., Miller JHLong-term results of femorotibial bypass with vein or polytetrafluoroethylene . Br J Surg. 1998;85(7):934-938.
4.
Ritter EF, Fata MM, Rudner AM, Klitzman B.Heparin bonding increases patency of long microvascular prostheses. Plast Reconstr Surg. 1998;101(1):142-146.
5.
Gosselin C., Vorp DA, Warty V., et al. ePTFE coating with fibrin glue, FGF-1, and heparin: Effect on retention of seeded endothelial cells. J Surg Res.1996;60(2):327-332.
Conklin BS, Wu H., Lin PH, Lumsden AB, Chen C.Basic fibroblast growth factor coating and endothelial cell seeding of a decellularized heparin-coated vascular graft. Artif Organs. 2004; 28(7):668-675.
8.
Cardinal KO, Bonnema GT, Hofer H., Barton JK, Williams SKTissue-engineered vascular grafts as in vitro blood vessel mimics for the evaluation of endothelialization of intravascular devices. Tissue Eng. 2006;12(12):3431-3438.
9.
Cho SW, Lim JE, Chu HS, et al. Enhancement of in vivo endothelialization of tissue-engineered vascular grafts by granulocyte colony-stimulating factor. J Biomed Mater Res A. 2006;76(2):252-263.
10.
Treasure CB, Klein JL, Weintraub WS, et al. Beneficial effects of cholesterol-lowering therapy on the coronary endothelium in patients with coronary artery disease. N Engl J Med. 1995; 332(8):481-487.
11.
Boodhwani M., Nakai Y., Voisine P., et al. High-dose atorvastatin improves hypercholesterolemic coronary endothelial dysfunction without improving the angiogenic response. Circulation. 2006; 114(1 suppl):402-408.
12.
Rioufol G., Gilard M., Finet G., Ginon I., Boschat J., André-Fouët X.Evolution of spontaneous atherosclerotic plaque rupture with medical therapy: long-term follow-up with intravascular ultrasound. Circulation . 2004;110(18):2875-2880.
13.
Di Sciascio G., Patti G., Pasceri V., Gaspardone A., Colonna G., Montinaro A.Efficacy of atorvastatin reload in patients on chronic statin therapy undergoing percutaneous coronary intervention: results of the ARMYDA-RECAPTURE (Atorvastatin for Reduction of Myocardial Damage During Angioplasty) Randomized Trial. J Am Coll Cardiol.2009;54(6):558-565.
14.
Briguori C. , Visconti G., Focaccio A., et al. Novel approaches for preventing or limiting events (Naples) II Trial impact of a single high loading dose of atorvastatin on periprocedural myocardial infarction. J Am Coll Cardiol.2009. [Epub ahead of print].
15.
Tousoulis D. , Andreou I., Antoniades C., Tentolouris C., Stefanadis C.Role of inflammation and oxidative stress in endothelial progenitor cell function and mobilization: Therapeutic implications for cardiovascular diseases. Atherosclerosis. 2008;201(2):236-247.
16.
Paraskevas KI, Liapis CD, Hamilton G., Mikhailidis DPAre statins an option in the management of abdominal aortic aneurysms? Vasc Endovascular Surg. 2008;42(2):128-134.
17.
Abbruzzese TA, Havens J., Belkin M., et al. Statin therapy is associated with improved patency of autogenous infrainguinal bypass grafts. J Vasc Surg. 2004;39(6):1178-1185.
18.
Christenson JTPreoperative lipid control with simvastatin reduces the risk for graft failure already 1 year after myocardial revascularization . Cardiovasc Surg. 2001;9(1):33-43.
19.
Llevadot J. , Murasawa S., Kureishi Y., et al. HMG-CoA reductase inhibitor mobilizes bone marrow-derived endothelial progenitor cells. J Clin Invest . 2001;108(3):399-405.
20.
Dimmeler S. , Aicher A., Vasa M., et al. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the pi 3-kinase/akt pathway. J Clin Invest. 2001;108(3):391-397.
21.
Scott SM, Barth MG, Gaddy LR, Ahl ET Jr.The role of circulating cells in the healing of vascular prostheses. J Vasc Surg. 1994; 19(4):585-593.
22.
Lahtinen M. , Blomberg P., Baliulis G., Carlsson F., Khamis H., Zemgulis V.In vivo h-VEGF165 gene transfer improves early endothelialization and patency in synthetic vascular grafts. Eur J Cardiothorac Surg.2007;31(3):383-390.
23.
Unver A., Perez M., Orellana N., Huang H., Rikihisa Y.Molecular and antigenic comparison of ehrlichia canis isolates from dogs, ticks, and a human in venezuela. J Clin Microbiol. 2001;39(8):2788-2793.
24.
Kusuyama T. , Omura T., Nishiya D., et al. The effects of HMGCoA reductase inhibitor on vascular progenitor cells. J Pharmacol Sci. 2006;101(4):344-349.
25.
Rehman J., Li J., Orschell CM, March KLPeripheral blood ‘‘Endothelial progenitor cells’’ are derived from monocyte/ macrophages and secrete angiogenic growth factors . Circulation. 2003;107(8):1164-1169.
26.
Kaushal S., Amiel GE, Guleserian KJ, et al. Functional small-diameter neovessels created using endothelial progenitor cells expanded ex vivo. Nat Med. 2001;7(9):1035-1040.
27.
Greisler HPArterial regeneration over absorbable prostheses . Arch Surg. 1982;117(11):1425-1431.
28.
Pasquinelli G., Freyrie A., Preda P., Curti T., D’Addato M., Laschi R.Healing of prosthetic arterial grafts. Scanning Microsc. 1990;4(2): 351-362.
29.
Zhang Z., Wang Z., Liu S., Kodama M.Pore size, tissue ingrowth, and endothelialization of small-diameter microporous polyurethane vascular prostheses. Biomaterials. 2004;25(1):177-187.
30.
Asahara T., Murohara T., Sullivan A., et al. Isolation of putative progenitor endothelial cells for angiogenesis . Science. 1997; 275(5302):964-967.
31.
Cho SW, Lim SH, Kim IK, et al. Small-diameter blood vessels engineered with bone marrow-derived cells. Ann Surg. 2005; 241(3):506-515.
32.
Werner N., Priller J., Laufs U., et al. Bone marrow-derived progenitor cells modulate vascular re- endothelialization and neointimal formation: effect of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition. Arterioscler Thromb Vasc Biol. 2002; 22(10):1567-1572.
33.
Crombez M., Chevallier P., Gaudreault RC, Petitclerc E., Mantovani D., Laroche G.Improving arterial prosthesis neo-endothelialization: Application of a proactive VEGF construct onto PTFE surfaces. Biomaterials. 2005;26(35):7402-7409.
34.
Randone B., Cavallaro G., Polistena A., et al. Dual role of VEGF in pretreated experimental EPTFE arterial grafts. J Surg Res. 2005; 127(2):70-79.
35.
Li X., Xu B.HMG-CoA reductase inhibitor regulates endothelial progenitor function through the phosphatidylinositol 3’-kinase/akt signal transduction pathway. Appl Biochem Biotechnol.2009; 157(3):545-553.
36.
Ishida A., Wu MH, Shi Q., et al. Dynamic changes of smooth muscle and endothelial markers in the early healing process of dacron vascular grafts in the dog, using RT-PCR . Int J Angiol. 2000;9(2): 107-110.
37.
Uchida C., Haas TLEvolving strategies in manipulating VEGF/ VEGFR signaling for the promotion of angiogenesis in ischemic muscle. Curr Pharm Des.2009;15(4):411-421.
38.
Payne TR, Oshima H., Okada M., et al. A relationship between vascular endothelial growth factor, angiogenesis, and cardiac repair after muscle stem cell transplantation into ischemic hearts . J Am Coll Cardiol. 2007;50(17):1677-1684.
39.
Nishimoto-Hazuku A., Hirase T., Ide N., et al. Simvastatin stimulates vascular endothelial growth factor production by hypoxia- inducible factor-1 alpha upregulation in endothelial cells. J Cardiovasc Pharmacol.2008;51(3):267-273.
40.
Wu H., Lu D., Jiang H., et al. Simvastatin-mediated upregulation of VEGF and BDNF, activation of the pi3k/ akt pathway, and increase of neurogenesis are associated with therapeutic improvement after traumatic brain injury. J Neurotrauma . 2008;25(2): 130-139.
Landmesser U. , Engberding N., Bahlmann FH, et al. Statin-induced improvement of endothelial progenitor cell mobilization, myocardial neovascularization, left ventricular function, and survival after experimental myocardial infarction requires endothelial nitric oxide synthase. Circulation. 2004;110(14): 1933-1939.
43.
Gonzalez-Fernandez F., Jimenez A., Lopez-Blaya A., et al. Cerivastatin prevents tumor necrosis factor-alpha-induced downregulation of endothelial nitric oxide synthase: role of endothelial cytosolic proteins. Atherosclerosis. 2001;155(1):61-70.
44.
Urbich C., Dernbach E., Zeiher AM, Dimmeler S.Double-edged role of statins in angiogenesis signaling. Circ Res. 2002;90(6): 737-744.
45.
Ariyoshi H. , Okuyama M., Okahara K., et al. Expanded polytetrafluoroethylene (ePTFE) vascular graft loses its thrombogenicity six months after implantation. Thromb Res. 1997;88(5): 427-433.
46.
Fatourou EM , Paraskevas KI, Seifalian AM, Hamilton G., Mikhailidis DPThe role of established and emerging risk factors in peripheral vascular graft occlusion. Expert Opin Pharmacother. 2007;8(7):901-911.
47.
Laufs U.Beyond lipid-lowering: effects of statins on endothelial nitric oxide. Eur J Clin Pharmacol. 2003;58(11):719-731.
