Detection of the '4977 bp' mitochondrial DNA deletion in human atherosclerotic lesions

The presence of the 4977 bp deletion ('common deletion') in the mitochondri al DNA (mtDNA) is associated with defects in the metabolic machinery acquir ed during ageing as a hallmark of a degenerative phenotype, We analysed 27 samples (18 from surgical patients and nine from autopsy cases) of DNA extr acted from smooth muscle cells of abdominal aorta fragments affected by ath erosclerotic lesions. The deletion was detected by PCR amplification-gel el ectrophoresis and characterized by sequencing of the PCR product. The mtDNA 'common deletion' was detected in all analysed samples. However, its level s were not particularly high, which may be ascribed to the fact that smooth muscle cells in atherosclerotic lesions have a lower energy requirement an d an appreciable proliferation rate, as compared for instance with cardiac myocytes, When the subjects were divided into two numerically equivalent ag e classes (60-72 Sears plus a 45-year-old subject versus 73-95 years), the deletion had significantly higher levels in the older subjects. Conversely, its presence did not correlate with source (surgical or autoptic), sex, ci garettes consumption, other clinical and anamnestic parameters or with the levels of adducts and 8-hydroxy-2'-deoxyguanosine measured in the nuclear D NA of the same samples, A previously unreported deletion of 5111 bp was add itionally found in the mtDNA from a 45-year-old woman. The origin of this l esion seems to be compatible with the slipped mispairing model proposed for the 'common deletion'.