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.
Similar content being viewed by others
References
Anitschkow N, Chalatow S (1913) Ueber experimentelle Cholesterinsteatose und ihre Bedeutung für die Entstehung einiger pathologischer Prozesse. Zentralbl Allg Pathol 24:1–9
Hanson GK, Holm J, Jonasson L (1989) Detection of activated T lymphocytes in the human atherosclerotic plaque. Am J Pathol 135(1):169–175
Kaisering C (1896) Über die Conservierung von Sammlungspräparaten mit Erhaltung der natürlichen Farben. Berlin Klin Wschr 33:775–777
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):1927–1937
Libby P, Ridker P, Maeri A (2002) Inflammation and atherosclerosis. Circulation 105(9)1135–1143
Lobstein J (1833) Traité d’Anatomie Pathologique, vol 2. Levrault, Paris
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):547–553
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):831–842
Nieto FJ (1998) Infections and atherosclerosis: new clues from an old hypothesis? Am J Epidemiol 148(10):937–948
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):1060–1065
Rokitansky C (1855) A manual of pathological anatomy. Blanchard and Lea, Philadelphia
Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362(6423):801–809
Ruffer MA (1911) On arterial lesions found in Egyptian mummies. J Pathol Bacteriol 15:453–462
Sandison AT (1962) Degenerative vascular disease in the Egyptian mummy. Med Hist 6:77–81
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):12–18
Steinberg D, Witztum JL (1990) Lipoproteins and atherogenesis: current concepts. JAMA 264(23):3047–3052
Virchow R (1971) Cellular pathology as based upon physiological and pathological histology (English translation of second German edition). JB, Lippincott, Philadelphia
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):1347–1350
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):76–80
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 36:1565–1579
Wick G, Knoflach M, Xu Q (2004) Autoimmune and inflammatory mechanisms in atherosclerosis. Annu Rev Immunol 22:361–403
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):1199–1207
Windaus A (1910) Ueber den Gehalt normaler und atheromatoeser Aorten an Cholesterol and Cholesterinester. Zeitschrift Physiol Chem 67:174–176
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):789–799
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):344–359
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):14–20
Zimmerman MR (1993) The paleopathology of the cardiovascular system. Texas Heart Inst J 20:252–257
Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352(16):1685–1695
Breslow JL (1996) Mouse models of atherosclerosis. Science 272:685–88
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):745–753
Sposito AC, Chapman MJ (2002) Statin therapy in acute coronary syndromes: mechanistic insight into clinical benefit. Arterioscler Thromb Vasc Biol 22(10):1524–1534
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):8549–8556
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):1206–1213
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):900–905
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):1158–1161
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):417–422
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mayerl, C., Lukasser, M., Sedivy, R. et al. Atherosclerosis research from past to present—on the track of two pathologists with opposing views, Carl von Rokitansky and Rudolf Virchow. Virchows Arch 449, 96–103 (2006). https://doi.org/10.1007/s00428-006-0176-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00428-006-0176-7