This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Salomon, R. N. Articles by Libby, P. Search for Related Content PubMed PubMed Citation Articles by Salomon, R. N. Articles by Libby, P.

American Journal of Pathology, Vol 138, 791-798, Copyright © 1991 by American Society for Investigative Pathology

REGULAR ARTICLES

Human coronary transplantation-associated arteriosclerosis. Evidence for a chronic immune reaction to activated graft endothelial cells

RN Salomon, CC Hughes, FJ Schoen, DD Payne, JS Pober and P Libby
Department of Pathology, New England Medical Center, Boston, Massachusetts.

Occlusive disease of coronary arteries of engrafted hearts is the major obstacle to long-term survival of human cardiac allografts. The pathogenesis of this process remains uncertain. The identity and localization of cells found in transplantation-associated arteriosclerosis lesions from human cardiac allografts were evaluated, and their expression of class II major histocompatibility complex (human leukocyte antigen-DR [HLA-DR]), surface molecules required for recognition of foreign cells by CD4+ T lymphocytes, was noted. Expanded intimas of transplanted coronary arteries contain T lymphocytes (both CD4+ and CD8+ in approximately equal number) and HLA-DR+ macrophages, both localized primarily in a ring immediately below the luminal endothelium, a distribution strikingly different from that in typical atherosclerosis. Coronary arterial endothelium from six of six transplanted hearts studied bore high levels of HLA-DR. Normal human arteries or usual atherosclerotic lesions have few if any HLA-DR+ endothelial cells. The significance of these findings was tested by evaluating the ability of HLA-DR+ arterial cells to interact with allogeneic T cells in vitro. Endothelial cells (but not smooth muscle cells) cultured from human arteries stimulated foreign CD4+ T cells to proliferate and augmented their secretion of interleukin-2. These findings suggest that ongoing stimulation of recipient T lymphocytes by HLA-DR+ endothelium of donor coronary arteries contributes to a sustained regional immune response. Consequent local release of cytokines may regulate smooth muscle cell proliferation and matrix accumulation within the coronary arteries of allografted hearts.

This article has been cited by other articles:

				R. Sheshgiri, V. Rao, L. C. Tumiati, R. Xiao, J. L. Prodger, M. Badiwala, C. Librach, and D. H. Delgado Progesterone Induces Human Leukocyte Antigen-G Expression in Vascular Endothelial and Smooth Muscle Cells Circulation, September 30, 2008; 118(14_suppl_1): S58 - S64. [Abstract] [Full Text] [PDF]

				B. P. Griffith, M. Haddad, and R. S. Poston Immunobiology of Heart and Heart-Lung Transplantation Card. Surg. Adult, January 1, 2008; 3(2008): 1513 - 1538. [Full Text]

				M. C. Cuffy, A. M. Silverio, L. Qin, Y. Wang, R. Eid, G. Brandacher, F. G. Lakkis, D. Fuchs, J. S. Pober, and G. Tellides Induction of Indoleamine 2,3-Dioxygenase in Vascular Smooth Muscle Cells by Interferon-{gamma} Contributes to Medial Immunoprivilege J. Immunol., October 15, 2007; 179(8): 5246 - 5254. [Abstract] [Full Text] [PDF]

				R. N. Mitchell and P. Libby Vascular Remodeling in Transplant Vasculopathy Circ. Res., April 13, 2007; 100(7): 967 - 978. [Abstract] [Full Text] [PDF]

				H. Xu, K. K. Dhanireddy, and A. D. Kirk Human Monocytes as Intermediaries between Allogeneic Endothelial Cells and Allospecific T Cells: A Role for Direct Scavenger Receptor-Mediated Endothelial Membrane Uptake in the Initiation of Alloimmunity J. Immunol., January 15, 2006; 176(2): 750 - 761. [Abstract] [Full Text] [PDF]

				P. Y. Hsue and D. D. Waters What a Cardiologist Needs to Know About Patients With Human Immunodeficiency Virus Infection Circulation, December 20, 2005; 112(25): 3947 - 3957. [Abstract] [Full Text] [PDF]

				A. C. Newby Dual Role of Matrix Metalloproteinases (Matrixins) in Intimal Thickening and Atherosclerotic Plaque Rupture Physiol Rev, January 1, 2005; 85(1): 1 - 31. [Abstract] [Full Text] [PDF]

				P. Y. Hsue, J. C. Lo, A. Franklin, A. F. Bolger, J. N. Martin, S. G. Deeks, and D. D. Waters Progression of Atherosclerosis as Assessed by Carotid Intima-Media Thickness in Patients With HIV Infection Circulation, April 6, 2004; 109(13): 1603 - 1608. [Abstract] [Full Text] [PDF]

				J. J. Yun, D. Whiting, M. P. Fischbein, A. Banerji, Y. Irie, D. Stein, M. C. Fishbein, A. E.I. Proudfoot, H. Laks, J. A. Berliner, et al. Combined Blockade of the Chemokine Receptors CCR1 and CCR5 Attenuates Chronic Rejection Circulation, February 24, 2004; 109(7): 932 - 937. [Abstract] [Full Text] [PDF]

				T. W. Kuijpers, M. Biezeveld, A. Achterhuis, I. Kuipers, J. Lam, C. E. Hack, A. E. Becker, and A. C. van der Wal Longstanding Obliterative Panarteritis in Kawasaki Disease: Lack of Cyclosporin A Effect Pediatrics, October 1, 2003; 112(4): 986 - 992. [Abstract] [Full Text] [PDF]

				G. Vassalli, A. Gallino, M. Weis, W. von Scheidt, L. Kappenberger, L.K. von Segesser, J.-J. Goy, and on behalf of the Working Group Microcirculation of Alloimmunity and nonimmunologic risk factors in cardiac allograft vasculopathy Eur. Heart J., July 1, 2003; 24(13): 1180 - 1188. [Abstract] [Full Text] [PDF]

				B. P. Griffith and R. S. Poston Immunobiology of Heart and Heart-Lung Transplantation Card. Surg. Adult, January 1, 2003; 2(2003): 1403 - 1426. [Full Text]

				R. W. Alexander Oxidized LDL Autoantibodies, Endothelial Dysfunction, and Transplant-Associated Arteriosclerosis Arterioscler. Thromb. Vasc. Biol., December 1, 2002; 22(12): 1950 - 1951. [Full Text] [PDF]

				J. C. Fang, S. Kinlay, D. Behrendt, H. Hikita, J. L. Witztum, A. P. Selwyn, and P. Ganz Circulating Autoantibodies to Oxidized LDL Correlate With Impaired Coronary Endothelial Function After Cardiac Transplantation Arterioscler. Thromb. Vasc. Biol., December 1, 2002; 22(12): 2044 - 2048. [Abstract] [Full Text] [PDF]

				L. L. Salazar Murphy and C. C. W. Hughes Endothelial Cells Stimulate T Cell NFAT Nuclear Translocation in the Presence of Cyclosporin A: Involvement of the wnt/Glycogen Synthase Kinase-3{beta} Pathway J. Immunol., October 1, 2002; 169(7): 3717 - 3725. [Abstract] [Full Text] [PDF]

				J. H. Li, M. S. Kluger, L. A. Madge, L. Zheng, A. L. M. Bothwell, and J. S. Pober Interferon-{gamma} Augments CD95(APO-1/Fas) and Pro-Caspase-8 Expression and Sensitizes Human Vascular Endothelial Cells to CD95-Mediated Apoptosis Am. J. Pathol., October 1, 2002; 161(4): 1485 - 1495. [Abstract] [Full Text] [PDF]

				N. Marx, B. Kehrle, K. Kohlhammer, M. Grub, W. Koenig, V. Hombach, P. Libby, and J. Plutzky PPAR Activators as Antiinflammatory Mediators in Human T Lymphocytes: Implications for Atherosclerosis and Transplantation-Associated Arteriosclerosis Circ. Res., April 5, 2002; 90(6): 703 - 710. [Abstract] [Full Text] [PDF]

				M. P. Fischbein, J. Yun, H. Laks, Y. Irie, M. C. Fishbein, B. Bonavida, and A. Ardehali Role of CD8+ lymphocytes in chronic rejection of transplanted hearts J. Thorac. Cardiovasc. Surg., April 1, 2002; 123(4): 803 - 809. [Abstract] [Full Text] [PDF]

				Y. Furukawa, P. Libby, J. L. Stinn, G. Becker, and R. N. Mitchell Cold Ischemia Induces Isograft Arteriopathy, but Does Not Augment Allograft Arteriopathy in Non-Immunosuppressed Hosts Am. J. Pathol., March 1, 2002; 160(3): 1077 - 1087. [Abstract] [Full Text] [PDF]

				V. Marti, I. Romeo, R. Aymat, J. Garcia, P. Guiteras, M. Ballester, N. Aminian, J. M. Caralps, and J. M. Auge Coronary endothelial dysfunction as a predictor of intimal thickening in the long term after heart transplantation J. Thorac. Cardiovasc. Surg., December 1, 2001; 122(6): 1174 - 1180. [Abstract] [Full Text] [PDF]

				J. Mestas and C. C. W. Hughes Endothelial Cell Costimulation of T Cell Activation Through CD58-CD2 Interactions Involves Lipid Raft Aggregation J. Immunol., October 15, 2001; 167(8): 4378 - 4385. [Abstract] [Full Text] [PDF]

				P. C. Grimm, P. Nickerson, J. Jeffery, R. C. Savani, J. Gough, R. M. McKenna, E. Stern, and D. N. Rush Neointimal and Tubulointerstitial Infiltration by Recipient Mesenchymal Cells in Chronic Renal-Allograft Rejection N. Engl. J. Med., July 12, 2001; 345(2): 93 - 97. [Abstract] [Full Text] [PDF]

				B. C. Berk Vascular Smooth Muscle Growth: Autocrine Growth Mechanisms Physiol Rev, July 1, 2001; 81(3): 999 - 1030. [Abstract] [Full Text] [PDF]

				M. S. Eisenberg, H. J. Chen, M. K. Warshofsky, R. R. Sciacca, H. S. Wasserman, A. Schwartz, and L. E. Rabbani Elevated Levels of Plasma C-Reactive Protein Are Associated With Decreased Graft Survival in Cardiac Transplant Recipients Circulation, October 24, 2000; 102(17): 2100 - 2104. [Abstract] [Full Text] [PDF]

				C. A. Slachta, V. Jeevanandam, B. Goldman, W. L. Lin, and C. D. Platsoucas Coronary Arteries from Human Cardiac Allografts with Chronic Rejection Contain Oligoclonal T Cells: Persistence of Identical Clonally Expanded TCR Transcripts from the Early Post-Transplantation Period (Endomyocardial Biopsies) to Chronic Rejection (Coronary Arteries) J. Immunol., September 15, 2000; 165(6): 3469 - 3483. [Abstract] [Full Text] [PDF]

				M. M. Mazanet, K. Neote, and C. C. W. Hughes Expression of IFN-Inducible T Cell {alpha} Chemoattractant by Human Endothelial Cells Is Cyclosporin A-Resistant and Promotes T Cell Adhesion: Implications for Cyclosporin A-Resistant Immune Inflammation J. Immunol., May 15, 2000; 164(10): 5383 - 5388. [Abstract] [Full Text] [PDF]

				E. Aptecar, E. Teiger, P. Dupouy, C. Benvenuti, M. J. Kern, J. Woscoboinik, S. Sediame, J. M. Pernes, A. Castaigne, D. Loisance, et al. Effects of bradykinin on coronary blood flow and vasomotion in transplant patients J. Am. Coll. Cardiol., May 1, 2000; 35(6): 1607 - 1615. [Abstract] [Full Text] [PDF]

				H. Dietrich, Y. Hu, Y. Zou, S. Dirnhofer, R. Kleindienst, G. Wick, and Q. Xu Mouse Model of Transplant Arteriosclerosis : Role of Intercellular Adhesion Molecule-1 Arterioscler. Thromb. Vasc. Biol., February 1, 2000; 20(2): 343 - 352. [Abstract] [Full Text] [PDF]

				Y. Furukawa, G. Becker, J. L. Stinn, K. Shimizu, P. Libby, and R. N. Mitchell Interleukin-10 (IL-10) Augments Allograft Arterial Disease : Paradoxical Effects of IL-10 in Vivo Am. J. Pathol., December 1, 1999; 155(6): 1929 - 1939. [Abstract] [Full Text] [PDF]

				M.-W. Hwang, A. Matsumori, Y. Furukawa, K. Ono, M. Okada, A. Iwasaki, M. Hara, and S. Sasayama FTY720, a New Immunosuppressant, Promotes Long-Term Graft Survival and Inhibits the Progression of Graft Coronary Artery Disease in a Murine Model of Cardiac Transplantation Circulation, September 21, 1999; 100(12): 1322 - 1329. [Abstract] [Full Text] [PDF]

				J.L Mehta and D.Y Li Inflammation in ischemic heart disease: Response to tissue injury or a pathogenetic villain? Cardiovasc Res, August 1, 1999; 43(2): 291 - 299. [Full Text] [PDF]

				P.F. Ludman, F. Lazem, M. Barbir, and M. Yacoub Incidence and clinical relevance of coronary calcification detected by electron beam computed tomography in heart transplant recipients Eur. Heart J., February 2, 1999; 20(4): 303 - 308. [Abstract] [PDF]

				J. Koglin, T. Glysing-Jensen, A. Raisanen-Sokolowski, and M. E. Russell Immune Sources of Transforming Growth Factor-ß1 Reduce Transplant Arteriosclerosis : Insight Derived From a Knockout Mouse Model Circ. Res., September 21, 1998; 83(6): 652 - 660. [Abstract] [Full Text] [PDF]

				S. Ravalli, A. Albala, M. Ming, M. Szabolcs, A. Barbone, R. E. Michler, and P. J. Cannon Inducible Nitric Oxide Synthase Expression in Smooth Muscle Cells and Macrophages of Human Transplant Coronary Artery Disease Circulation, June 16, 1998; 97(23): 2338 - 2345. [Abstract] [Full Text] [PDF]

				D. B. Cines, E. S. Pollak, C. A. Buck, J. Loscalzo, G. A. Zimmerman, R. P. McEver, J. S. Pober, T. M. Wick, B. A. Konkle, B. S. Schwartz, et al. Endothelial Cells in Physiology and in the Pathophysiology of Vascular Disorders Blood, May 15, 1998; 91(10): 3527 - 3561. [Full Text] [PDF]

				A. C. Nicholson and D. P. Hajjar Herpesviruses in Atherosclerosis and Thrombosis : Etiologic Agents or Ubiquitous Bystanders? Arterioscler. Thromb. Vasc. Biol., March 1, 1998; 18(3): 339 - 348. [Abstract] [Full Text] [PDF]

				G. Vassalli, A. Gallino, W. Kiowski, Z. Jiang, M. Turina, and O. M. Hess Reduced Coronary Flow Reserve During Exercise in Cardiac Transplant Recipients Circulation, February 4, 1997; 95(3): 607 - 613. [Abstract] [Full Text]

				S. Ravalli, M. Szabolcs, A. Albala, R. E. Michler, and P. J. Cannon Increased Immunoreactive Endothelin-1 in Human Transplant Coronary Artery Disease Circulation, November 1, 1996; 94(9): 2096 - 2102. [Abstract] [Full Text]

				K. B. Lemstrom, A. K. Raisanen-Sokolowski, P. J. Hayry, and P. K. Koskinen Triple Drug Immunosuppression Significantly Reduces Aortic Allograft Arteriosclerosis in the Rat Arterioscler. Thromb. Vasc. Biol., April 1, 1996; 16(4): 553 - 564. [Abstract] [Full Text]

				S. F. Davis, A. C. Yeung, I. T. Meredith, F. Charbonneau, P. Ganz, A. P. Selwyn, and T. J. Anderson Early Endothelial Dysfunction Predicts the Development of Transplant Coronary Artery Disease at 1 Year Posttransplant Circulation, February 1, 1996; 93(3): 457 - 462. [Abstract] [Full Text]

				C. A. Labarrere, D. Pitts, D. R. Nelson, and W. P. Faulk Vascular Tissue Plasminogen Activator and the Development of Coronary Artery Disease in Heart-Transplant Recipients N. Engl. J. Med., October 26, 1995; 333(17): 1111 - 1116. [Abstract] [Full Text] [PDF]

				T. Nakagawa, G. K. Sukhova, E. Rabkin, G. L. Winters, F. J. Schoen, and P. Libby Acute Rejection Accelerates Graft Coronary Disease in Transplanted Rabbit Hearts Circulation, August 15, 1995; 92(4): 987 - 993. [Abstract] [Full Text]

				A. Ardehali, H. Laks, D. C. Drinkwater, E. Ziv, and T. A. Drake Vascular Cell Adhesion Molecule–1 Is Induced on Vascular Endothelia and Medial Smooth Muscle Cells in Experimental Cardiac Allograft Vasculopathy Circulation, August 1, 1995; 92(3): 450 - 456. [Abstract] [Full Text]

				P. Libby Molecular Bases of the Acute Coronary Syndromes Circulation, June 1, 1995; 91(11): 2844 - 2850. [Full Text]

				M. C. Deng, S. Bell, P. Huie, F. Pinto, S. A. Hunt, E. B. Stinson, R. Sibley, B. M. Hall, and H. A. Valantine Cardiac Allograft Vascular Disease : Relationship to Microvascular Cell Surface Markers and Inflammatory Cell Phenotypes on Endomyocardial Biopsy Circulation, March 15, 1995; 91(6): 1647 - 1654. [Abstract] [Full Text]

				S. Ravalli, C. C. Marboe, V. D. D'Agati, R. E. Michler, E. Sigal, and P. J. Cannon Immunohistochemical Demonstration of 15-Lipoxygenase in Transplant Coronary Artery Disease Arterioscler. Thromb. Vasc. Biol., March 1, 1995; 15(3): 340 - 348. [Abstract] [Full Text]

				T. Hirozane, A. Matsumori, Y. Furukawa, and S. Sasayama Experimental Graft Coronary Artery Disease in a Murine Heterotopic Cardiac Transplant Model Circulation, January 15, 1995; 91(2): 386 - 392. [Abstract] [Full Text]

				C. A. E. O'Blenes, C. Kinnear, and M. Rabinovitch Tumor Necrosis Factor-{alpha} Induces Fibronectin Synthesis in Coronary Artery Smooth Muscle Cells by a Nitric Oxide-Dependent Posttranscriptional Mechanism Circ. Res., July 6, 2001; 89(1): 26 - 32. [Abstract] [Full Text] [PDF]

				N. Marx, B. Kehrle, K. Kohlhammer, M. Grub, W. Koenig, V. Hombach, P. Libby, and J. Plutzky PPAR Activators as Antiinflammatory Mediators in Human T Lymphocytes: Implications for Atherosclerosis and Transplantation-Associated Arteriosclerosis Circ. Res., April 5, 2002; 90(6): 703 - 710. [Abstract] [Full Text] [PDF]

				C. Y. Wang, S. P. Mazer, K. Minamoto, S. Takuma, S. Homma, M. Yellin, L. Chess, A. Fard, S. L. Kalled, M. C. Oz, et al. Suppression of Murine Cardiac Allograft Arteriopathy by Long-Term Blockade of CD40-CD154 Interactions Circulation, April 2, 2002; 105(13): 1609 - 1614. [Abstract] [Full Text] [PDF]