| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 142, 1927-1937, Copyright © 1993 by American Society for Investigative Pathology
REGULAR ARTICLES |
R Kleindienst, Q Xu, J Willeit, FR Waldenberger, S Weimann and G Wick
Institute for General and Experimental Pathology, University of Innsbruck Medical School, Austria.
Our previous work revealed the presence of a great number of activated T lymphocytes in early human atherosclerotic lesions, and we were able to induce atherosclerosis in normocholesterolemic rabbits by immunization with Mycobacterium tuberculosis heat-shock protein (HSP) 65. We hypothesized this latter phenomenon to arise from cross- reactivity of mycobacterial HSP 65 with the endogenously expressed homologous 60-kd form of this stress protein. To study HSP 60 expression and the phenotype of intima infiltrating T lymphocytes relative to the T cell receptor (TCR) in human atherosclerotic lesions, specimens of aorta, carotid arteries, and internal mammary arteries and veins, as well as saphenous veins and vena cava from 27 subjects, aged 23 to 80 years, were examined using immunohistochemical and immunofluorescence techniques on serial frozen tissue sections. HSP 60 was detected on endothelium, smooth muscle cells, and/or mononuclear cells of all carotid and aortic specimens, whereas vessels of smaller diameter, serving as reference specimens for normal intima without atherosclerotic lesions and mononuclear infiltration, showed no detectable expression of this stress protein. Furthermore, although the majority of CD3+ cells within the mononuclear cell infiltrates of atherosclerotic lesions bear the alpha/beta TCR, a considerable portion also consisted of gamma/delta TCR+ cells. Thus, 9.7% of T cells in the transition zone between normal intima and fatty streaks carry the gamma/delta TCR, a proportion that decreases to 6.6% and 4.3% in fatty streaks and atherosclerotic plaques, respectively. We conclude that the intensity of HSP 60 expression correlates positively with the atherosclerotic severity and that most lymphocytes participating in atherogenesis bear the alpha/beta TCR, although gamma/delta TCR+ cells are also enriched in atherosclerotic lesions. Expression of HSP 60 by intimal cells, caused, eg, by hemodynamic shear forces, may be responsible for recruitment of HSP-sensitized T cells, thus leading to the induction of an initiating inflammatory process in atherosclerosis. Other risk factors, such as high serum cholesterol levels, contribute to the final outcome of the disease.
This article has been cited by other articles:
 |
|
 |
|
  X. Zhang, M.-A. He, L. Cheng, L. Zhou, H. Zeng, J. Wang, F. Wang, Y. Chen, F. B. Hu, and T. Wu Joint Effects of Antibody to Heat Shock Protein 60, Hypertension, and Diabetes on Risk of Coronary Heart Disease in Chinese Clin. Chem., June 1, 2008; 54(6): 1046 - 1052. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Herrmann, S. M. Soares, L. O. Lerman, and A. Lerman Potential role of the ubiquitin-proteasome system in atherosclerosis aspects of a protein quality disease. J. Am. Coll. Cardiol., May 27, 2008; 51(21): 2003 - 2010. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.H.M. van Puijvelde, T. van Es, E.J.A. van Wanrooij, K.L.L. Habets, P. de Vos, R. van der Zee, W. van Eden, Th. J.C. van Berkel, and J. Kuiper Induction of Oral Tolerance to HSP60 or an HSP60-Peptide Activates T Cell Regulation and Reduces Atherosclerosis Arterioscler. Thromb. Vasc. Biol., December 1, 2007; 27(12): 2677 - 2683. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. VAN EDEN, G. WICK, S. ALBANI, and I. COHEN Stress, Heat Shock Proteins, and Autoimmunity: How Immune Responses to Heat Shock Proteins Are to Be Used for the Control of Chronic Inflammatory Diseases Ann. N.Y. Acad. Sci., October 1, 2007; 1113(1): 217 - 237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. AYADA, K. YOKOTA, K. KOBAYASHI, Y. SHOENFELD, E. MATSUURA, and K. OGUMA Chronic Infections and Atherosclerosis Ann. N.Y. Acad. Sci., June 1, 2007; 1108(1): 594 - 602. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-K. L. Robertson and G. K Hansson T Cells in Atherogenesis: For Better or For Worse? Arterioscler. Thromb. Vasc. Biol., November 1, 2006; 26(11): 2421 - 2432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V P van Halm, M C Slot, M T Nurmohamed, J W Cohen Tervaert, B A C Dijkmans, and A E Voskuyl Antibodies against human 60 kDa heat shock protein are not associated with cardiovascular disease in patients with rheumatoid arthritis Ann Rheum Dis, May 1, 2006; 65(5): 590 - 594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Xiao, K. Mandal, G. Schett, M. Mayr, G. Wick, F. Oberhollenzer, J. Willeit, S. Kiechl, and Q. Xu Association of Serum-Soluble Heat Shock Protein 60 With Carotid Atherosclerosis: Clinical Significance Determined in a Follow-Up Study Stroke, December 1, 2005; 36(12): 2571 - 2576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K Mandal, G Foteinos, M Jahangiri, and Q Xu Role of antiheat shock protein 60 autoantibodies in atherosclerosis Lupus, September 1, 2005; 14(9): 742 - 746. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Benagiano, M. M. D'Elios, A. Amedei, A. Azzurri, R. van der Zee, A. Ciervo, G. Rombola, S. Romagnani, A. Cassone, and G. Del Prete Human 60-kDa Heat Shock Protein Is a Target Autoantigen of T Cells Derived from Atherosclerotic Plaques J. Immunol., May 15, 2005; 174(10): 6509 - 6517. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. VanderLaan and C. A. Reardon Thematic review series: The Immune System and Atherogenesis. The unusual suspects:an overview of the minor leukocyte populations in atherosclerosis J. Lipid Res., May 1, 2005; 46(5): 829 - 838. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Elhage, P. Gourdy, L. Brouchet, J. Jawien, M.-J. Fouque, C. Fievet, X. Huc, Y. Barreira, J. C. Couloumiers, J.-F. Arnal, et al. Deleting TCR{alpha}{beta}+ or CD4+ T Lymphocytes Leads to Opposite Effects on Site-Specific Atherosclerosis in Female Apolipoprotein E-Deficient Mice Am. J. Pathol., December 1, 2004; 165(6): 2013 - 2018. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Martin-Ventura, M. C. Duran, L. M. Blanco-Colio, O. Meilhac, A. Leclercq, J.-B. Michel, O. N. Jensen, S. Hernandez-Merida, J. Tunon, F. Vivanco, et al. Identification by a Differential Proteomic Approach of Heat Shock Protein 27 as a Potential Marker of Atherosclerosis Circulation, October 12, 2004; 110(15): 2216 - 2219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Dyugovskaya, P. Lavie, and L. Lavie Phenotypic and Functional Characterization of Blood {gamma}{delta} T Cells in Sleep Apnea Am. J. Respir. Crit. Care Med., July 15, 2003; 168(2): 242 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Gao and M.-F. Tsan Recombinant Human Heat Shock Protein 60 Does Not Induce the Release of Tumor Necrosis Factor {alpha} from Murine Macrophages J. Biol. Chem., June 13, 2003; 278(25): 22523 - 22529. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Metzler, R. Abia, M. Ahmad, F. Wernig, O. Pachinger, Y. Hu, and Q. Xu Activation of Heat Shock Transcription Factor 1 in Atherosclerosis Am. J. Pathol., May 1, 2003; 162(5): 1669 - 1676. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Xu Role of Heat Shock Proteins in Atherosclerosis Arterioscler. Thromb. Vasc. Biol., October 1, 2002; 22(10): 1547 - 1559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Pockley Heat Shock Proteins, Inflammation, and Cardiovascular Disease Circulation, February 26, 2002; 105(8): 1012 - 1017. [Full Text] [PDF]
|
|
|
|
|
|
G. K. Hansson Immune Mechanisms in Atherosclerosis Arterioscler. Thromb. Vasc. Biol., December 1, 2001; 21(12): 1876 - 1890. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Kanwar, J. R. Kanwar, D. Wang, D. J. Ormrod, and G. W. Krissansen Temporal Expression of Heat Shock Proteins 60 and 70 at Lesion-Prone Sites During Atherogenesis in ApoE-Deficient Mice Arterioscler. Thromb. Vasc. Biol., December 1, 2001; 21(12): 1991 - 1997. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Wuttge, P. Eriksson, A. Sirsjo, G. K. Hansson, and S. Stemme Expression of Interleukin-15 in Mouse and Human Atherosclerotic Lesions Am. J. Pathol., August 1, 2001; 159(2): 417 - 423. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. Hammerer-Lercher, J. Mair, J. Bonatti, S. B.C. Watzka, B. Puschendorf, and S. Dirnhofer Hypoxia induces heat shock protein expression in human coronary artery bypass grafts Cardiovasc Res, April 1, 2001; 50(1): 115 - 124. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Li, K. M. Kolltveit, L. Tronstad, and I. Olsen Systemic Diseases Caused by Oral Infection Clin. Microbiol. Rev., October 1, 2000; 13(4): 547 - 558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Mayr, S. Kiechl, J. Willeit, G. Wick, and Q. Xu Infections, Immunity, and Atherosclerosis : Associations of Antibodies to Chlamydia pneumoniae, Helicobacter pylori, and Cytomegalovirus With Immune Reactions to Heat-Shock Protein 60 and Carotid or Femoral Atherosclerosis Circulation, August 22, 2000; 102(8): 833 - 839. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Pockley, R. Wu, C. Lemne, R. Kiessling, Ulf de Faire, and J. Frostegard Circulating Heat Shock Protein 60 Is Associated With Early Cardiovascular Disease Hypertension, August 1, 2000; 36(2): 303 - 307. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Xu, G. Schett, H. Perschinka, M. Mayr, G. Egger, F. Oberhollenzer, J. Willeit, S. Kiechl, and G. Wick Serum Soluble Heat Shock Protein 60 Is Elevated in Subjects With Atherosclerosis in a General Population Circulation, July 4, 2000; 102(1): 14 - 20. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-W. Hochleitner, E.-O. Hochleitner, P. Obrist, T. Eberl, A. Amberger, Q. Xu, R. Margreiter, and G. Wick Fluid Shear Stress Induces Heat Shock Protein 60 Expression in Endothelial Cells In Vitro and In Vivo Arterioscler. Thromb. Vasc. Biol., March 1, 2000; 20(3): 617 - 623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Xu, S. Kiechl, M. Mayr, B. Metzler, G. Egger, F. Oberhollenzer, J. Willeit, and G. Wick Association of Serum Antibodies to Heat-Shock Protein 65 With Carotid Atherosclerosis : Clinical Significance Determined in a Follow-Up Study Circulation, September 14, 1999; 100(11): 1169 - 1174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Epstein, Y. F. Zhou, and J. Zhu Infection and Atherosclerosis : Emerging Mechanistic Paradigms Circulation, July 27, 1999; 100 (4): e20 - e28. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Alcouffe, S. Caspar-Bauguil, V. Garcia, R. Salvayre, M. Thomsen, and H. Benoist Oxidized low density lipoproteins induce apoptosis in PHA-activated peripheral blood mononuclear cells and in the Jurkat T-cell line J. Lipid Res., July 1, 1999; 40(7): 1200 - 1210. [Abstract] [Full Text]
|
|
|
|
|
|
M. Mayr, B. Metzler, S. Kiechl, J. Willeit, G. Schett, Q. Xu, and G. Wick Endothelial Cytotoxicity Mediated by Serum Antibodies to Heat Shock Proteins of Escherichia coli and Chlamydia pneumoniae : Immune Reactions to Heat Shock Proteins as a Possible Link Between Infection and Atherosclerosis Circulation, March 30, 1999; 99(12): 1560 - 1566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Zugel and S. H. E. Kaufmann Role of Heat Shock Proteins in Protection from and Pathogenesis of Infectious Diseases Clin. Microbiol. Rev., January 1, 1999; 12(1): 19 - 39. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Waltner–Romen, G. Falkensammer, W. Rabl, and G. Wick A Previously Unrecognized Site of Local Accumulation of Mononuclear Cells: the Vascular-associated Lymphoid Tissue J. Histochem. Cytochem., December 1, 1998; 46(12): 1347 - 1350. [Abstract] [Full Text]
|
|
|
|
|
|
D. P. Strachan, M. A. Mendall, D. Carrington, B. K. Butland, J. W. G. Yarnell, P. M. Sweetnam, and P. C. Elwood Relation of Helicobacter pylori Infection to 13-Year Mortality and Incident Ischemic Heart Disease in the Caerphilly Prospective Heart Disease Study Circulation, September 29, 1998; 98(13): 1286 - 1290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kol, G. K. Sukhova, A. H. Lichtman, and P. Libby Chlamydial Heat Shock Protein 60 Localizes in Human Atheroma and Regulates Macrophage Tumor Necrosis Factor-{alpha} and Matrix Metalloproteinase Expression Circulation, July 28, 1998; 98(4): 300 - 307. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Metzler, G. Schett, R. Kleindienst, R. van der Zee, T. Ottenhoff, A. Hajeer, R. Bernstein, Q. Xu, and G. Wick Epitope Specificity of Anti–Heat Shock Protein 65/60 Serum Antibodies in Atherosclerosis Arterioscler. Thromb. Vasc. Biol., March 1, 1997; 17(3): 536 - 541. [Abstract] [Full Text]
|
|
|
|
|
|
J. Frostegard, C. Lemne, B. Andersson, R. van der Zee, R. Kiessling, and U. de Faire Association of Serum Antibodies to Heat-Shock Protein 65 With Borderline Hypertension Hypertension, January 1, 1997; 29(1): 40 - 44. [Abstract] [Full Text]
|
|
|
|
|
|
J. R. Guyton and K. F. Klemp Development of the Lipid-Rich Core in Human Atherosclerosis Arterioscler. Thromb. Vasc. Biol., January 1, 1996; 16(1): 4 - 11. [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
