Advertisement

Virchows Archiv

, Volume 449, Issue 1, pp 96–103 | Cite as

Atherosclerosis research from past to present—on the track of two pathologists with opposing views, Carl von Rokitansky and Rudolf Virchow

  • Christina Mayerl
  • Melanie Lukasser
  • Roland Sedivy
  • Harald Niederegger
  • Ruediger Seiler
  • Georg Wick
Original Article

Abstract

It is now clear that inflammation plays a key role in atherogenesis. As a matter of fact, signs of inflammation of atherosclerotic plaques have been observed for centuries and also constituted the basis for a fierce controversy in the 19th century between the prominent Austrian pathologist Carl von Rokitansky and his German counterpart, Rudolf Virchow. While the former attributed a secondary role to these inflammatory arterial changes, Virchow considered them to be of primary importance. We had the unique opportunity to address this controversy by investigating atherosclerotic specimens from autopsies performed by Carl von Rokitansky up to 178 years ago. Twelve atherosclerotic arteries originally collected between the years 1827 to 1885 were selected from the Collectio Rokitansky of the Federal Museum of Pathological Anatomy, Vienna Medical University. Using modern sophisticated immunohistochemical and immunofluorescence techniques, it was shown that various cellular intralesional components, as well as extracellular matrix proteins, were preserved in the historic atherosclerotic specimens. Most importantly, CD3 positive cells were abundant in early lesions, thus, rather supporting Virchows’s view, that inflammation is an initiating factor in atherogenesis. Furthermore, we hope to have opened a new and intriguing possibility to study various pathological conditions using valuable historical specimens.

Keywords

Atherosclerosis Inflammation Historical material 

Notes

Acknowledgements

We want to thank Ruth Pfeilschifter-Resch and the medical technologists at the Department of Clinical Pathology in Vienna for preparing paraffin sections as well as Ilona Lengenfelder for assistance in the preparation of figures and Dr. Beatrix Patzak for consulting in sample selection. The Clinical Department of Plastic and Reconstructive Surgery, University Hospital Innsbruck, Austria and Dr. Felix Offner from the Department of Pathology, County Hospital Feldkirch, kindly provided recent control tissue. The authors want to acknowledge the Austrian Science Fund (FWF-project no.14741 to G.W.) and the European Union (Molecular basis of vascular events leading to thrombotic stroke, MOLSTROKE; LSHM-CT-2004-005206) for supporting the project.

References

  1. 1.
    Anitschkow N, Chalatow S (1913) Ueber experimentelle Cholesterinsteatose und ihre Bedeutung für die Entstehung einiger pathologischer Prozesse. Zentralbl Allg Pathol 24:1–9Google Scholar
  2. 2.
    Hanson GK, Holm J, Jonasson L (1989) Detection of activated T lymphocytes in the human atherosclerotic plaque. Am J Pathol 135(1):169–175PubMedGoogle Scholar
  3. 3.
    Kaisering C (1896) Über die Conservierung von Sammlungspräparaten mit Erhaltung der natürlichen Farben. Berlin Klin Wschr 33:775–777Google Scholar
  4. 4.
    Kleindienst R, Xu Q, Willeit J, Waldenberger FR, Weimann S, Wick G (1993) Immunology of atherosclerosis: demonstration of heat shock protein 60 expression and T-lymphocytes bearing alpha/beta or gamma/delta receptor in human atherosclerotic lesions. Am J Pathol 142(6):1927–1937PubMedGoogle Scholar
  5. 5.
    Libby P, Ridker P, Maeri A (2002) Inflammation and atherosclerosis. Circulation 105(9)1135–1143CrossRefPubMedGoogle Scholar
  6. 6.
    Lobstein J (1833) Traité d’Anatomie Pathologique, vol 2. Levrault, ParisGoogle Scholar
  7. 7.
    Millonig G, Schwentner C, Müller P, Mayerl C, Wick G (2001) The vascular-associated lymphoid tissue: a new site of local immunity. Curr Opin Lipidol 12(5):547–553CrossRefPubMedGoogle Scholar
  8. 8.
    Navab M, Berliner JA, Watson AD, Hama SY, Territo MC, Lusis AJ, Shih DM, Van Lenten BJ, Frank JS, Demer LL, Edwards PA, Fogelman AM (1996) The Yin and Yang of oxidation in the development of the fatty streak. A review based on the 1994 George Lyman Duff Memorial Lecture. Arterioscler Thromb Vasc Biol 16(7):831–842PubMedGoogle Scholar
  9. 9.
    Nieto FJ (1998) Infections and atherosclerosis: new clues from an old hypothesis? Am J Epidemiol 148(10):937–948PubMedGoogle Scholar
  10. 10.
    Perschinka H, Mayr M, Millonig G, Mayerl C, van der Zee R, Morrison SG, Morrison RP, Xu Q, Wick G (2003) Cross-Reactive B-Cell Epitopes of Microbial and Human Heat Shock Protein 60/65 in Atherosclerosis. Arterioscler Thromb Vasc Biol 23(6):1060–1065CrossRefPubMedGoogle Scholar
  11. 11.
    Rokitansky C (1855) A manual of pathological anatomy. Blanchard and Lea, PhiladelphiaGoogle Scholar
  12. 12.
    Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362(6423):801–809CrossRefPubMedGoogle Scholar
  13. 13.
    Ruffer MA (1911) On arterial lesions found in Egyptian mummies. J Pathol Bacteriol 15:453–462CrossRefGoogle Scholar
  14. 14.
    Sandison AT (1962) Degenerative vascular disease in the Egyptian mummy. Med Hist 6:77–81Google Scholar
  15. 15.
    Sedivy R, Patzak B (2002) Pancreatic diseaes past and present: a historical examination of exhibition specimens from the Collectio Rokitansky in Vienna. Virchows Arch 441(1):12–18CrossRefPubMedGoogle Scholar
  16. 16.
    Steinberg D, Witztum JL (1990) Lipoproteins and atherogenesis: current concepts. JAMA 264(23):3047–3052CrossRefPubMedGoogle Scholar
  17. 17.
    Virchow R (1971) Cellular pathology as based upon physiological and pathological histology (English translation of second German edition). JB, Lippincott, PhiladelphiaGoogle Scholar
  18. 18.
    Waltner-Romen M, Falkensammer G, Rabl W, Wick G (1998) A previously unrecognized site of local accumulation of mononuclear cells: the vascular-associated lymphoid tissue. J Histochem Cytochem 46(12):1347–1350PubMedGoogle Scholar
  19. 19.
    Wick G, Haller M, Timpl R, Cleve H, Ziegelmayer G (1980) Mummies from Peru: demonstration of antigenic determinants of collagen in the skin. Int Arch Allergy Appl Immunol 62(1):76–80PubMedGoogle Scholar
  20. 20.
    Wick G, Kalischnig G, Maurer H, Mayerl C, Mueller PU (2001) Really old—Paleoimmunology: immunohistochemical analysis of extracellular matrix proteins in historic and pre-historic material. Exp Gerontol 36:1565–1579CrossRefPubMedGoogle Scholar
  21. 21.
    Wick G, Knoflach M, Xu Q (2004) Autoimmune and inflammatory mechanisms in atherosclerosis. Annu Rev Immunol 22:361–403CrossRefPubMedGoogle Scholar
  22. 22.
    Wick G, Romen M, Amberger A, Metzler B, Mayr M, Falkensammer G, Xu Q (1997) Atherosclerosis, autoimmunity, and vascular-associated lymphoid tissue. FASEB J 11(13):1199–1207PubMedGoogle Scholar
  23. 23.
    Windaus A (1910) Ueber den Gehalt normaler und atheromatoeser Aorten an Cholesterol and Cholesterinester. Zeitschrift Physiol Chem 67:174–176Google Scholar
  24. 24.
    Xu Q, Dietrich H, Steiner HJ, Gown AM, Schoel B, Mikuz G, Kaufmann SH (1992) Induction of arteriosclerosis in normocholesterolemic rabbits by immunization with heat shock protein 65. Arterioscler Thromb Vasc Biol 12(7):789–799Google Scholar
  25. 25.
    Xu Q, Oberhuber G, Gruschwitz M, Wick G (1990) Immunology of atherosclerosis: cellular composition and major histocompatibility complex class II antigen expression in aortic intima, fatty streaks and atherosclerotic plaques in young and aged human specimens. Clin Immunol Immunopathol 56(3):344–359CrossRefPubMedGoogle Scholar
  26. 26.
    Xu Q, Schett G, Perschinka H, Mayr M, Egger G, Oberhollenzer F, Willeit J, Kiechl S, Wick G (2000) Serum soluble Heat Shock Protein 60 is elevated in subjects with atherosclerosis in a general population. Circulation 102(1):14–20PubMedGoogle Scholar
  27. 27.
    Zimmerman MR (1993) The paleopathology of the cardiovascular system. Texas Heart Inst J 20:252–257Google Scholar
  28. 28.
    Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352(16):1685–1695CrossRefPubMedGoogle Scholar
  29. 29.
    Breslow JL (1996) Mouse models of atherosclerosis. Science 272:685–88PubMedCrossRefGoogle Scholar
  30. 30.
    Caligiuri G, Nicoletti A, Poirier B, Hansson GK (2002) Protective immunity against atherosclerosis carried by B cells of hypercholesterolemic mice. J Clin Invest 109(6):745–753CrossRefPubMedGoogle Scholar
  31. 31.
    Sposito AC, Chapman MJ (2002) Statin therapy in acute coronary syndromes: mechanistic insight into clinical benefit. Arterioscler Thromb Vasc Biol 22(10):1524–1534CrossRefPubMedGoogle Scholar
  32. 32.
    Jurgens G, Xu Q, Huber L, Bock G, Howanietz H, Wick G, Traill KN (1989) Promotion of lymphocyte growth by high density lipoproteins (HDL). Physiological significance of the HDL binding site. J Biol Chem 264(15):8549–8556PubMedGoogle Scholar
  33. 33.
    Foteinos G, Afzal AR, Mandal K, Jahangiri M, Xu Q (2005) Anti-heat shock protein 60 autoantibodies induce atherosclerosis in apolipoprotein E-deficient mice via endothelial damage. Circulation 112(8):1206–1213CrossRefPubMedGoogle Scholar
  34. 34.
    George J, Afek A, Gilburd B, Shoenfeld Y, Harats D (2001) Cellular and humoral immune responses to heat shock protein 65 are both involved in promoting fatty-streak formation in LDL-receptor deficient mice. J Am Coll Cardiol 38(3):900–905CrossRefPubMedGoogle Scholar
  35. 35.
    Edfeldt K, Swedenborg J, Hansson GK, Yan ZQ (2002) Expression of toll-like receptors in human atherosclerotic lesions: a possible pathway for plaque activation. Circulation 105(10):1158–1161PubMedGoogle Scholar
  36. 36.
    Tupin E, Nicoletti A, Elhage R, Rudling M, Ljunggren HG, Hansson GK, Berne GP (2004) CD1d-dependent activation of NKT cells aggravates atherosclerosis. J Exp Med 199(3):417–422CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Christina Mayerl
    • 1
  • Melanie Lukasser
    • 1
  • Roland Sedivy
    • 2
  • Harald Niederegger
    • 1
  • Ruediger Seiler
    • 3
  • Georg Wick
    • 1
  1. 1.Division of Experimental Pathophysiology and Immunology, Department BiocenterInnsbruck Medical UniversityInnsbruckAustria
  2. 2.Department of Clinical PathologyUniversity Hospital ViennaViennaAustria
  3. 3.Department of Vascular SurgeryUniversity Hospital InnsbruckInnsbruckAustria

Personalised recommendations