Mitochondrial Damage Leads to Atherosclerosis

Scott Ballinger
University of Texas Medical Branch
R03ES09318

Background: Reactive species (RS) are made up of a group of reactive oxygen and nitrogen species that can alter the biological functions of essential molecules such as lipids, proteins, and DNA. Numerous studies have linked RS with the development of atherosclerotic disease which remains the leading cause of death in the Western world. Although the exact sequence of events in this process is yet to be determined, RS likely play an important role in vascular cell dysfunction and atherosclerosis probably through oxidative damage to the mitochondrial genome. In this study, the investigators examined the contribution of mitochondrial oxidant generation and DNA damage to the progression of atherosclerotic lesions in human arterial specimens and a mouse model prone to atherosclerosis.

Advance: Mitochondrial DNA damage correlated with the extent of atherosclerosis in the human tissue and in the susceptible mice. The DNA alterations were seen prior to the development of atherogenesis in the mice suggesting a causative relationship. In addition, mice deficient in manganese superoxide dismutase, a mitochondrial antioxidant enzyme, exhibited early increases in mitochondrial DNA damage and a phenotype of accelerated atherogenesis.

Implications: These studies suggest that mitochondrial DNA damage may result from RS production in vascular tissues and may also be an early event in the development of atherosclerosis. Additional research confirming these results may lead to earlier detection of individuals at risk for atherosclerotic disease and improved methods to prevent of reverse the formation of atherosclerotic plaques through the use of antioxidant therapies.

Citation: Ballinger SW, Paterson C, Knight-Lozano CA, Burow DL, Conklin CA, Hu A, Reuf J, Horaist C, Lebovitz R, Hunter GC, McIntyre K, and Runge MS. Mitochondrial Integrity and Function in Atherogenesis. Circulation 2002; 106:544-549.