Pathogenesis of atherosclerosis: infectious versus immune pathogenesis. A new concept.
A novel concept for the pathogenesis of atherosclerosis is presented that obviates the need to search for a causative infectious agent. It is shown that LDL stranded in the subendothelium is transformed by enzymatic (non-oxidative) modification to yield an entity with complement- and macrophage-activating properties. This primarily serves to clear the stranded lipoprotein from tissues. However, sustained overactivation of complement and macrophages occurs when LDL-deposition is too extensive. A chronic inflammation then ensuing initiates and promotes the pathology of the atherosclerotic lesion. Atherosclerosis is thus a special form of an immunopathological disease which evolves through overactivation of the most archaic effector components of the immune system by altered self.
Bhakdi
S
S
Institute of Medical Microbiology and Hygiene, Mainz, Germany. makowiec@mail.uni-mainz.de
D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000209:etiology* / Q000276:immunology* / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002690:Chlamydia Infections / Q000150:complications* / Q000276:immunology; D002692:Chlamydia trachomatis / Q000276:immunology; D016993:Chlamydophila pneumoniae / Q000276:immunology; D003167:Complement Activation; D003165:Complement System Proteins / Q000276:immunology / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000502:physiology; D009000:Monocytes / Q000276:immunology / Q000502:physiology; D011817:Rabbits
D000907:Antibodies, Bacterial; D000924:Anticholesteremic Agents; D008077:Lipoproteins, LDL; D003165:Complement System Proteins; D002097:C-Reactive Protein