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.