ATHEROSCLEROSIS AS AN AUTOIMMUNE CONDITION

Atherosclerosis is a multifactorial vascular disorder responsible for the highest rate of mortality in the western world. During the last de cades, research on this disease has primarily focused on the role of l ipids, which are essential to the formation of lesions in the vascular intima that ultimately leads to clinically apparent atherosclerotic p laques. More recently, several anecdotal findings have indicated the p ossible involvement of the immune system in the process of atherogenes is. In particular, the appearance of immunocompetent cells as well as humoral antibodies in the intima in the early stages of disease develo pment supports the view of an inflammatory component in this disorder. In addition to the search for lipid-associated antigens that might en tail full-blown atherosclerosis, other candidate antigens capable of i nducing an immune response in the vascular wall have also been explore d. Within the probable group of antigens for immune responsiveness, he at shock protein (hsp) 60/65 became a serious candidate, upon observat ion that immunization of rabbits with this protein led to arterioscler otic changes of the aortic intima. In the last few years we have estab lished this rabbit model for immunologic investigations of atheroscler osis and, in parallel, examined the pathogenesis of human atherosclero sis with regard to hsp 60/65 immune reactivity. Currently available da ta point to an autoimmune induction of early inflammatory arterioscler otic changes triggered by a cellular and humoral immune reaction to st ress-induced hsp 60-expressing areas of the endothelial cells.