An important role in atherogenesis is played by oxidative stress, which may be induced by common risk factors. Mitochondria are both sources and targets of reactive oxygen species, and there is growing evidence that mitochondrial dysfunction may be a relevant intermediate mechanism by which cardiovascular risk factors lead to the formation of vascular lesions. Mitochondrial DNA is probably the most sensitive cellular target of reactive oxygen species. Damage to mitochondrial DNA correlates with the extent of atherosclerosis. Several cardiovascular risk factors are demonstrated causes of mitochondrial damage. Oxidized low density lipoprotein and hyperglycemia may induce the production of reactive oxygen species in mitochondria of macrophages and endothelial cells.
There is a wide consensus that atherosclerosis (ATS) is an inflammatory disease associated with lipid and protein oxidation in the vascular wall. At sites of inflammation, the local cellular environment is enriched with cytokines, chemoactractant chemokines and reactive oxygen species (ROS), such as superoxide anion, mainly produced by the activated leukocytes adhering to the endothelium. Excess ROS and reactive nitrogen species (RNS) generation has been associated with vascular lesion formation and functional defects. ROS and RNS free radicals are molecules or molecular fragments containing one or more unpaired electrons in atomic or molecular orbitals. The unpaired electrons give the radicals a high degree of reactivity.
Common cardiovascular risk factors could be involved in this process by adversely affecting the function of endothelial mitochondria, and growing evidence supports the hypothesis that mitochondrial dysfunction may be the most important unifying mechanism explaining the atherogenic action of major cardiovascular risk factors. This review will discuss the molecular mechanisms by which atherosclerotic risk factors could lead to mitochondrial dysfunction and subsequent vascular impairment.