Mitochondrial dysfunction as an initiating event in atherogenesis: a plausible hypothesis.

It is now widely accepted that oxidant stress and the ensuing endothelial dysfunction play a key role in the pathogenesis of atherosclerosis and cardiovascular diseases. The mitochondrial respiratory chain is the major source of reactive oxygen species as byproducts of normal cell respiration. Mitochondria may also be important targets for reactive oxygen species, which may damage mitochondrial lipids, enzymes and DNA with following mitochondrial dysfunction. Free cholesterol, oxidized low-density lipoprotein and glycated high-density lipoprotein are further possible causes of mitochondrial dysfunction and/or apoptosis. Moreover, in patients with mitochondrial diseases, vascular complications are commonly observed at an early age, often in the absence of traditional risk factors for atherosclerosis. We propose that mitochondrial dysfunction, besides endothelial dysfunction, represents an important early step in the chain of events leading to atherosclerotic disease.