Infections may be causal in the pathogenesis of atherosclerosis.

There is a universal lack of exposure response between degree of lipid lowering and the outcome in clinical and angiographic trials questioning the current view on atherogenesis. However, there are numerous observations and experiments suggesting that microorganisms may play a causal role. A clue is the fact that the lipoproteins constitute an innate immune system by binding and inactivating microorganisms and their toxic products through formation of circulating complexes. Their size may increase in the presence of hyperhomocysteinemia because homocysteine reacts with low-density lipoprotein (LDL) to form homocysteinylated LDL aggregates. Autoantibodies against homocysteinylated or oxidized LDL may also enhance the aggregation. Because of the high extracapillary pressure, such aggregates may obstruct arterial vasa vasorum producing ischemia and cell death within the arterial wall leading to the creation of a vulnerable plaque. The many epidemiological observations, clinical findings and laboratory experiments that conflict with the cholesterol hypothesis are in good accordance with ours.