Antigen-tailored therapy based on the inflammatory theory of atherosclerosis.
In recent years, considerable data has been provided to support the role of the immune system in atherosclerosis. These reports came from studies involving knockout murine models of atherosclerosis and human subjects. The notion that inflammatory mechanisms are operable in atherogenesis has fueled a series of studies demonstrating that autoimmune responses are also evident in the atherosclerotic lesions and appear to influence the initiation and progression of the plaque. The principal autoantigens that have been suggested as potential triggers of autoimmune responses in atherosclerosis are modified forms of low-density lipoproteins, heat shock proteins and beta2 glycoprotein I. Immunization against these antigens influenced the generation of lesions and adoptive transfer studies of lymphocytes reactive to some of these antigens have also been demonstrated to enhance the growth of the plaques. The realization that autoimmune-like responses may play a role in the progression of atherosclerotic lesions has paved the way for exciting modes of manipulating lesions, irrespective of the effect on the lipid profile. Thus, recent studies indicate that oral tolerance with antigens or derivatives could suppress the respective immune responses and reduce the extent of the lesions in transgenic atherosclerosis-prone mice. These observations should be further explored and if validated, could represent novel modalities for influencing atherogenessis in humans.
Harats
Dror
D
Vascular Biogenics Ltd, 6, Jonathan Netanyahu St., Or Yehuda, 60376 Israel. dror@vbl.co.il
George
Jacob
J
D000284:Administration, Oral; D000818:Animals; D050197:Atherosclerosis / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology*; D015551:Autoimmunity; D004195:Disease Models, Animal; D006023:Glycoproteins / Q000008:administration & dosage / Q000276:immunology; D006360:Heat-Shock Proteins / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007114:Immunization; D007249:Inflammation / Q000276:immunology*; D008077:Lipoproteins, LDL / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D053482:beta 2-Glycoprotein I
D001324:Autoantigens; D006023:Glycoproteins; D006360:Heat-Shock Proteins; D008077:Lipoproteins, LDL; D053482:beta 2-Glycoprotein I; C099252:oxidized low density lipoprotein