Mitochondrial DNA Damage, Oxidative Stress and Atherosclerosis: Where There is Smoke There is not Always Fire
Atherosclerosis is an insidious disease which can remain undetected for decades before manifesting, sometimes lethally, in the form of a stroke or myocardial infarction. With over 900,000 Americans experiencing a heart attack annually1, there is a strong need to develop better treatments or preventative measures, but these will necessitate a better understanding of the underlying process. Most evidence suggests that atherosclerosis is initiated by chronic endothelial injury in response to the accumulation of low-density lipoprotein (LDL) and oxidized-LDL in the vessel wall, which stimulates an inflammatory response2. Although the involvement of elevated circulating lipids and oxidative stress are well recognized in this process (Figure 1), critical questions remain. These include the question of what causes the atherosclerotic plaque to worsen progressively rather than to resolve, and what causes relatively innocuous, stable plaques to transform into unstable, "vulnerable" plaques, which are liable to rupture and lead to thrombus formation.
- Received July 4, 2013.
- Accepted July 5, 2013.