Arterial wall oxygenation, oxyradicals, and atherosclerosis

The oxygen supply of inner media and thickened intima of atherosclerosis prone arteries depends largely on diffusion from the endothelium. Conditions which increase wall thickness and oxygen diffusion or reduce oxygen transmissibility produce hypoxia and steep PO2 gradients within the wall. Cerebral injury and myocardial reperfusion studies indicate that intermittent hypoxia and steep PO2 gradients lead to oxyradical formation and tissue damage. Products of lipid and sterol peroxidation are found in atherosclerotic plaques and can be generated by arterial wall cells in culture. It is likely that peroxidation occurs directly within the arterial wall. Sufficient oxyradical generation occurs during normal oxygen metabolism that local scavenger mechanisms are required to avoid tissue damage. Experimental hypertension, hyperlipemia and balloon injury produce medial hypoxia with steep PO2 gradients and redistribution of the pattern of arterial wall antioxidant enzymes. This suggests that minor deviations from normal arterial wall anatomy and function can lead to oxyradicals which can be directly injurious and can amplify the atherogenic potential of lipoprotein infiltration.