The oxidative stress hypothesis of atherosclerosis: cause or product?

The oxidative stress hypothesis postulates that endogenous free radicals of unknown origin, possibly derived from mural cells, oxidize low density lipoproteins and that oxidation products are allegedly responsible for initiation and progression of atherosclerosis. The thesis fails to explain its topography, site specific severity and the iatrogenic and experimental hemodynamic induction of atherosclerosis under conditions complying with the logic of Koch's postulates. Free radicals are generated by biomechanical scission of macromolecules and polymers, the biophysical mechanism underlying bioengineering fatigue in atherogenesis with oxidative damage a secondary, contributory factor to mural pathology. The plentiful supply of antioxidants negates oxidative stress as the dominant factor in atherogenesis.