Advertisement

Early inflammatory-immunological lesions in juvenile atherosclerosis from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY)-study

  • Gunda Millonig
    Affiliations
    Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria

    Institute for General and Experimental Pathology, University of Innsbruck, Fritz-Pregl-Strasse 3, 6020 Innsbruck, Austria
    Search for articles by this author
  • Gray T Malcom
    Affiliations
    Department of Pathology, Louisiana State University, New Orleans, LA, USA
    Search for articles by this author
  • Georg Wick
    Correspondence
    Corresponding author. Tel.: +43-512-507-3100; fax: +43-512-507-2867
    Affiliations
    Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria

    Institute for General and Experimental Pathology, University of Innsbruck, Fritz-Pregl-Strasse 3, 6020 Innsbruck, Austria
    Search for articles by this author

      Abstract

      The Pathobiological Determinants of Atherosclerosis in Youth (PDAY)-study gave insight into the correlation between the classical risk factors for atherosclerosis development, such as hypercholesterolemia, hyperglycemia, high blood pressure and smoking in young Americans. We now present immunohistochemical data showing that immunological-inflammatory signs represent the first step towards atherosclerosis development in the arteries of young adults. In previous publications, we coined the term ‘vascular-associated lymphoid tissue’ (VALT) for the accumulation of mononuclear cells at regions of the arterial wall in healthy children and adolescents that are predisposed to the development of atherosclerotic lesions later in life if risk factors are present. In the present communication, we intended to close the gap between data from atherosclerotic arteries and those of healthy young children studied previously by our group. The PDAY-study comprising 15–34-year-old Americans who had no clinical symptoms of cardiovascular diseases offered a good basis for our intention. We document that inflammatory activity was found in all specimens, represented by activated T-lymphocytes, dendritic cells, macrophages and aberrant MHC class II expression in the intima. We therefore demonstrated that immunological-inflammatory cells are present in the earliest stages of atherogenesis in 15–34-year-old subjects, arguing in favour of an initiating role of the immune system in atherosclerosis development.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Wick G.
        • Kleindienst R.
        • Hermann D.
        • Xu Q.
        Is atherosclerosis an autoimmune disease?.
        Trends Food Sci. Technol. 1992; 3: 114-119
        • Wick G.
        • Schett G.
        • Amberger A.
        • Kleindienst R.
        • Xu Q.
        Is atherosclerosis an immunologically mediated disease?.
        Immunol. Today. 1995; 16: 27-33
        • Xu Q.B.
        • Oberhuber G.
        • Gruschwitz M.
        • Wick G.
        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. 1990; 56: 344-359
        • Kleindienst R.
        • Xu Q.
        • Willeit J.
        • Waldenberger F.R.
        • Weimann S.
        • Wick G.
        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. 1993; 142: 1927-1937
        • Xu Q.
        • Kiechl S.
        • Mayr M.
        • et al.
        Association of serum antibodies to heat-shock protein 65 with carotid atherosclerosis: clinical significance determined in a follow-up study (see comments).
        Circulation. 1999; 100: 1169-1174
        • Mayr M.
        • Metzler B.
        • Kiechl S.
        • et al.
        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. 1999; 99: 1560-1566
        • Xu Q.
        • Willeit J.
        • Marosi M.
        • et al.
        Association of serum antibodies to heat-shock protein 65 with carotid atherosclerosis (see comments).
        Lancet. 1993; 341: 255-259
        • George J.
        • Shoenfeld Y.
        • Afek A.
        • et al.
        Enhanced fatty streak formation in C57BL/6J mice by immunization with heat shock protein-65.
        Arterioscler. Thromb. Vasc. Biol. 1999; 19: 505-510
        • George J.
        • Afek A.
        • Gilburd B.
        • et al.
        Hyperimmunization of apo-E-deficient mice with homologous malondialdehyde low-density lipoprotein suppresses early atherogenesis.
        Atherosclerosis. 1998; 138: 147-152
        • Waltner-Romen M.
        • Falkensammer G.
        • Rabl W.
        • Wick G.
        A previously unrecognized site of local accumulation of mononuclear cells. The vascular-associated lymphoid tissue.
        J. Histochem. Cytochem. 1998; 46: 1347-1350
        • Wick G.
        • Romen M.
        • Amberger A.
        • et al.
        Atherosclerosis, autoimmunity, and vascular-associated lymphoid tissue.
        FASEB J. 1997; 11: 1199-1207
        • McGill Jr, H.C.
        • McMahan C.A.
        • Tracy R.E.
        • et al.
        Relation of a postmortem renal index of hypertension to atherosclerosis and coronary artery size in young men and women. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group.
        Arterioscler. Thromb. Vasc. Biol. 1998; 18: 1108-1118
        • McGill Jr, H.C.
        • McMahan C.A.
        • Malcom G.T.
        • Oalmann M.C.
        • Strong J.P.
        Effects of serum lipoproteins and smoking on atherosclerosis in young men and women. The PDAY Research Group. Pathobiological Determinants of Atherosclerosis in Youth.
        Arterioscler. Thromb. Vasc. Biol. 1997; 17: 95-106
        • Xu Q.B.
        • Oberhuber G.
        • Gruschwitz M.
        • Wick G.
        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. 1990; 56: 344-359
        • Bobryshev Y.V.
        • Watanabe T.
        Subset of vascular dendritic cells transforming into foam cells in human atherosclerotic lesions.
        Cardiovasc. Pathol. 1997; 6: 321-331
        • Xu Q.
        • Dietrich H.
        • Steiner H.J.
        • et al.
        Induction of arteriosclerosis in normocholesterolemic rabbits by immunization with heat shock protein 65.
        Arterioscler. Thromb. 1992; 12: 789-799
        • Botti T.P.
        • Amin H.
        • Hiltscher L.
        • Wissler R.W.
        A comparison of the quantitation of macrophage foam cell populations and the extent of apolipoprotein E deposition in developing atherosclerotic lesions in young people: high and low serum thiocyanate groups as an indication of smoking. PDAY Research Group. Pathobiological Determinants of Atherosclerosis in Youth.
        Atherosclerosis. 1996; 124: 191-202
        • Kuo C.C.
        • Grayston J.T.
        • Campbell L.A.
        • Goo Y.A.
        • Wissler R.W.
        • Benditt E.P.
        Chlamydia pneumoniae (TWAR) in coronary arteries of young adults (15–34 years old).
        Proc. Natl. Acad. Sci. U.S.A. 1995; 92: 6911-6914