Arteriosclerosis and Thrombosis, Vol 13, 609-617, Copyright © 1993 by American Heart Association

ARTICLES

Cell proliferation in human arteriovenous fistulas used for hemodialysis

M Rekhter, S Nicholls, M Ferguson and D Gordon
Department of Pathology, University of Michigan, Ann Arbor 48109-0602.

The long-term patency of arteriovenous (AV) fistulas created for hemodialysis of renal-failure patients is usually measured in months, particularly when polytetrafluoroethylene (PTFE) material is interposed between the artery and vein. This is due to the rapid development of intimal hyperplastic lesions in the anastomosis region of the PTFE graft material with the vein. We studied the proliferative patterns in seven human AV fistulas removed at the time of fistula revision. Cell proliferation was determined by using an antibody to the proliferating cell nuclear antigen (PCNA), and specific cell types were identified by immunochemical reagents for smooth muscle cells, monocytes/macrophages, monocytes, lymphocytes, and endothelial cells. All venous segments exhibited a markedly hyperplastic intima. Vascularization of the intima and media by capillary-sized vessels was found. The main intimal cellular component was smooth muscle. Macrophages were usually seen around microvessels, and many also populated the perigraft region of the adventitia. In contrast to human atherosclerotic lesions, high rates of cell proliferation were observed in these fistulas. PCNA indices (percentage of cells that were PCNA positive [mean +/- SD]) were as follows: intima 17.7 +/- 11.3%, media 24 +/- 11.2%, and adventitia 20 +/- 11.6%. However, the distribution of PCNA-positive cells was not uniform. Instead, the PCNA index in microvessel- containing intimal fields was five to six times that of avascular fields (28.9 +/- 10.6% versus 4.9 +/- 4.5%, respectively, p < 0.001). Double immunolabeling revealed a large proportion of PCNA-positive microvascular endothelial cells and surrounding pericyte-like smooth muscle cells, as well as smooth muscle cells without visual connection to either microvessels or the lumen.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				S. Misra, A. A. Fu, K. D. Misra, J. F. Glockner, and D. Mukhopadhyay Wall Shear Stress Measurement Using Phase Contrast Magnetic Resonance Imaging With Phase Contrast Magnetic Resonance Angiography in Arteriovenous Polytetrafluoroethylene Grafts Angiology, August 1, 2009; 60(4): 441 - 447. [Abstract] [PDF]

				S. Misra, A. A. Fu, A. Puggioni, K. M. Karimi, J. N. Mandrekar, J. F. Glockner, L. A. Juncos, B. Anwer, A. M. McGuire, and D. Mukhopadhyay Increased shear stress with upregulation of VEGF-A and its receptors and MMP-2, MMP-9, and TIMP-1 in venous stenosis of hemodialysis grafts Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H2219 - H2230. [Abstract] [Full Text] [PDF]

				A. Chu, E. T. Ordonez, and M. K. Hellerstein Measurement of mouse vascular smooth muscle and atheroma cell proliferation by 2H2O incorporation into DNA Am J Physiol Cell Physiol, November 1, 2006; 291(5): C1014 - C1021. [Abstract] [Full Text] [PDF]

				B. S Dixon, G. J Beck, L. M Dember, T. A Depner, J. J Gassman, T. Greene, J. Himmelfar, L. G Hunsicker, J. S Kaufman, J. H Lawson, et al. Design of the Dialysis Access Consortium (DAC) Aggrenox prevention of access stenosis trial Clinical Trials, October 1, 2005; 2(5): 400 - 412. [Abstract] [PDF]

				Z. Luo, G. Y. Akita, T. Date, C. Treleaven, K. A. Vincent, D. Woodcock, S. H. Cheng, R. J. Gregory, and C. Jiang Adenovirus-Mediated Expression of {beta}-Adrenergic Receptor Kinase C-Terminus Reduces Intimal Hyperplasia and Luminal Stenosis of Arteriovenous Polytetrafluoroethylene Grafts in Pigs Circulation, April 5, 2005; 111(13): 1679 - 1684. [Abstract] [Full Text] [PDF]

				J. I. Rotmans, P. M.T. Pattynama, H. J.M. Verhagen, I. Hino, E. Velema, G. Pasterkamp, and E. S.G. Stroes Sirolimus-Eluting Stents to Abolish Intimal Hyperplasia and Improve Flow in Porcine Arteriovenous Grafts: A 4-Week Follow-Up Study Circulation, March 29, 2005; 111(12): 1537 - 1542. [Abstract] [Full Text] [PDF]

				A. Absood, A. Furutani, T. Kawamura, and L. M. Graham A comparison of oxidized LDL-induced collagen secretion by graft and aortic SMCs: role of PDGF Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1200 - H1206. [Abstract] [Full Text] [PDF]

				P. Ravani, G. Brunori, S. Mandolfo, G. Cancarini, E. Imbasciati, D. Marcelli, and F. Malberti Cardiovascular Comorbidity and Late Referral Impact Arteriovenous Fistula Survival: A Prospective Multicenter Study J. Am. Soc. Nephrol., January 1, 2004; 15(1): 204 - 209. [Abstract] [Full Text] [PDF]

				R. Garcia-Pajares, J. R. Polo, {i. e.}n. Flores, E. Gonzalez-Tabares, and J. V. Solis Upper Arm Polytetrafluoroethylene Grafts for Dialysis Access. Analysis of Two Different Graft Sizes: 6 mm and 6-8 mm Vascular and Endovascular Surgery, September 1, 2003; 37(5): 335 - 343. [Abstract] [PDF]

				K. A. Nath, S. K. R. Kanakiriya, J. P. Grande, A. J. Croatt, and Z. S. Katusic Increased Venous Proinflammatory Gene Expression and Intimal Hyperplasia in an Aorto-Caval Fistula Model in the Rat Am. J. Pathol., June 1, 2003; 162(6): 2079 - 2090. [Abstract] [Full Text] [PDF]

				R. de Graaf, R. Dammers, T. Vainas, A. P. G. Hoeks, and J. H. M. Tordoir Detection of cell-cycle regulators in failed arteriovenous fistulas for haemodialysis Nephrol. Dial. Transplant., April 1, 2003; 18(4): 814 - 818. [Abstract] [Full Text] [PDF]

				G. X. Zaleski, B. Funaki, J. Rosenblum, J. Theoharis, and J. Leef Metallic Stents Deployed in Synthetic Arteriovenous Hemodialysis Grafts Am. J. Roentgenol., June 1, 2001; 176(6): 1515 - 1519. [Abstract] [Full Text] [PDF]

				N. IKEGAYA, T. YAMAMOTO, A. TAKESHITA, T. WATANABE, K. YONEMURA, T. MIYAJI, K. OHISHI, M. FURUHASHI, Y. MARUYAMA, and A. HISHIDA Elevated Erythropoietin Receptor and Transforming Growth Factor-{beta}1 Expression in Stenotic Arteriovenous Fistulae Used for Hemodialysis J. Am. Soc. Nephrol., May 1, 2000; 11(5): 928 - 935. [Abstract] [Full Text]

				W. J. Weninger, G. B. Muller, C. Reiter, S. Meng, and S. U. Rabl Intimal Hyperplasia of the Infant Parasellar Carotid Artery : A Potential Developmental Factor in Atherosclerosis and SIDS Circ. Res., November 12, 1999; 85(10): 970 - 975. [Abstract] [Full Text] [PDF]

				D. Beasley and A. L. Cooper Constitutive expression of interleukin-1alpha precursor promotes human vascular smooth muscle cell proliferation Am J Physiol Heart Circ Physiol, March 1, 1999; 276(3): H901 - H912. [Abstract] [Full Text] [PDF]

				L. Wu, P. Chen, J.-J. Hwang, L. W. Barsky, K. I. Weinberg, A. Jong, and V. A. Starnes RNA Antisense Abrogation of MAT1 Induces G1 Phase Arrest and Triggers Apoptosis in Aortic Smooth Muscle Cells J. Biol. Chem., February 26, 1999; 274(9): 5564 - 5572. [Abstract] [Full Text] [PDF]

				R. Brandl, T. Richter, K. Haug, M. G. Wilhelm, P. C. Maurer, and W. Nathrath Topographic Analysis of Proliferative Activity in Carotid Endarterectomy Specimens by Immunocytochemical Detection of the Cell Cycle–Related Antigen Ki-67 Circulation, November 18, 1997; 96(10): 3360 - 3368. [Abstract] [Full Text]

				D. L. Wood, D. Panda, T. R. Wiernicki, L. Wilson, M. A. Jordan, and J. P. Singh Inhibition of Mitosis and Microtubule Function through Direct Tubulin Binding by a Novel Antiproliferative Naphthopyran LY290181 Mol. Pharmacol., September 1, 1997; 52(3): 437 - 444. [Abstract] [Full Text]

				M. Kearney, A. Pieczek, L. Haley, D. W. Losordo, V. Andres, R. Schainfeld, K. Rosenfield, and J. M. Isner Histopathology of In-Stent Restenosis in Patients With Peripheral Artery Disease Circulation, April 15, 1997; 95(8): 1998 - 2002. [Abstract] [Full Text]

				L. Hofstra, J. H.M. Tordoir, P. J.E.H.M. Kitslaar, A. P.G. Hoeks, and M. J.A.P. Daemen Enhanced Cellular Proliferation in Intact Stenotic Lesions Derived From Human Arteriovenous Fistulas and Peripheral Bypass Grafts: Does It Correlate With Flow Parameters? Circulation, September 15, 1996; 94(6): 1283 - 1290. [Abstract] [Full Text]

				K. H. Barth, R. Virmani, J. Froelich, T. Takeda, S. V. Lossef, J. Newsome, R. Jones, and D. Lindisch Paired Comparison of Vascular Wall Reactions to Palmaz Stents, Strecker Tantalum Stents, and Wallstents in Canine Iliac and Femoral Arteries Circulation, June 15, 1996; 93(12): 2161 - 2169. [Abstract] [Full Text]

				R. Riessen, T. N. Wight, C. Pastore, C. Henley, and J. M. Isner Distribution of Hyaluronan During Extracellular Matrix Remodeling in Human Restenotic Arteries and Balloon-Injured Rat Carotid Arteries Circulation, March 15, 1996; 93(6): 1141 - 1147. [Abstract] [Full Text]

				X. Girerd, G. London, P. Boutouyrie, J.-J. Mourad, M. Safar, and S. Laurent Remodeling of the Radial Artery in Response to a Chronic Increase in Shear Stress Hypertension, March 1, 1996; 27(3): 799 - 803. [Abstract] [Full Text]

				S. M. Schwartz, D. deBlois, and E. R. M. O'Brien The Intima : Soil for Atherosclerosis and Restenosis Circ. Res., September 1, 1995; 77(3): 445 - 465. [Full Text]

				R. L. Geary, N. Koyama, T. W. Wang, S. Vergel, and A. W. Clowes Failure of Heparin to Inhibit Intimal Hyperplasia in Injured Baboon Arteries : The Role of Heparin-Sensitive and -Insensitive Pathways in the Stimulation of Smooth Muscle Cell Migration and Proliferation Circulation, June 15, 1995; 91(12): 2972 - 2981. [Abstract] [Full Text]