Heat Shock Protein 60 in Human Diseases and Disorders by Alexzander A. A. Asea & Punit Kaur

Author:Alexzander A. A. Asea & Punit Kaur
Language: eng
Format: epub
ISBN: 9783030231545
Publisher: Springer International Publishing

13.1.1 The Past: How HSP60 Became an Atherogenic Molecule

In the 1980s, members of our group were studying the role of changes in lipid metabolism on the phenotypic and functional age-dependent alterations of lymphoid cells (Traill et al. 1990). In the course of this work, we observed an increased expression of low-density lipoprotein (LDL)-receptors on the surface of lymphocytes from elderly donors and an increased plasma membrane viscosity due to an elevated molar ratio of free cholesterol to phospholipids (Huber et al. 1991). For determining cell membrane viscosity, we used a modified method employed for measurements of single cells by flow cytometry (Böck et al. 1989). We then finally decoded the defects of the intracellular lipid metabolism responsible for the age-dependent alterations of lymphoid cell function (Stulnig et al. 1995). In 1988, we presented these data at a Meeting on Aging that we organized in Seefeld, Tyrol. There, we also briefly alluded to the possible role of our observations in the relative loss of immunological self-recognition and thus increased autoimmunity – our major field of expertise – in older age. Later at the bar, some of our colleagues teased us saying that we looked at every immunological finding from the perspective of autoimmunologists and that we would perhaps end up claiming that even atherosclerosis was an autoimmune disease. Interestingly, we had already earlier floated thoughts along these lines, albeit without even planning or performing any experimental work.

Back in the lab after the conference, we seriously discussed applying our expertise in autoimmunology to tackling this problem. This decision was further promoted by our knowledge as immunopathologists that hallmarks of inflammation had already been described more than a century earlier (Mayerl et al. 2006). As a matter of fact, this phenomenon had recently been “rediscovered” by several groups (Ross 1999; Ridker et al. 2002; Hansson and Libby 2006; Jongstra-Bilen et al. 2006). However, most of these latter studies were performed on patients and experimental animals with fully developed, late-stage atherosclerosis, i.e. a situation that was not of prime interest to us. Pathohistological or proteomic analyses of atherosclerotic plaques certainly revealed a panoply of cellular elements and expressed proteins that reflect a situation far from the stage of the initiation of the lesion (Danesh et al. 1997; Daugherty et al. 1997). In contrast to these studies, our own work on organ-specific and systemic autoimmune diseases always focused on two specific issues, viz. (a) what are the first cells/molecules that initiate the disease, and (b) how can our data be interpreted from an evolutionary viewpoint?

At the beginning of our project on The Immunology of Atherosclerosis, we therefore first performed pathohistological studies comparing early to late human atherosclerotic lesions (Xu et al. 1990). In contrast to the then prevalent dogma, these studies showed that T cells preceded the appearance of macrophages/foam cells in early lesions, while later the number of foam cells by far exceeded that of lymphoid cells. These observations were later confirmed in further studies on specimens of early lesions (Millonig et al. 2002).

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