Oxidants and antioxidants

Abstract

Risk factors are generally first identified in epidemiological studies and the mechanisms through which they cause disease subsequently analyzed in cellular and animal models. Although this is partly true also for low levels of antioxidant vitamins as being a cardiovascular risk factor, the concept of increased oxidative stress in atherosclerosis originates mainly from experimental studies. The idea that oxidation of low density lipoprotein (LDL) in the arterial wall plays a key role in the development of atherosclerosis has gained impressive support from molecular studies in cell culture as well as from experiments performed in different animal models of atherosclerosis and subsequently also by extensive epidemiology (1,2). However, the outcome of both primary and secondary randomized intervention trials in which the effect of antioxidant vitamins on cardiovascular disease has been studied have so far largely been disappointing (3). Keeping in mind the complexity of cardiovascular disease, this may not be entirely surprising. We have for many years been well aware of the fact that smoking, diabetes, and hypertension are major risk factors for cardiovascular disease, but our knowledge of the molecular mechanism by which they cause disease remains incomplete and superficial. It may turn out to be equally difficult to identify proper treatments for specific disease mechanisms even if they are well characterized at the molecular level, such as in the case of lipid oxidation and atherosclerosis. This chapter will summarize the experimental studies on which the concept of LDL oxidation as a key mechanism in atherosclerosis is based as well as the epidemiological and intervention studies performed to assess the role of antioxidants in cardiovascular disease.