Detection of the '4977 bp' mitochondrial DNA deletion in human atherosclerotic lesions.
The presence of the 4977 bp deletion ('common deletion') in the mitochondrial DNA (mtDNA) is associated with defects in the metabolic machinery acquired during ageing as a hallmark of a degenerative phenotype. We analysed 27 samples (18 from surgical patients and nine from autopsy cases) of DNA extracted from smooth muscle cells of abdominal aorta fragments affected by atherosclerotic lesions. The deletion was detected by PCR amplification gel electrophoresis and characterized by sequencing of the PCR product. The mtDNA 'common deletion' was detected in all analysed samples. However, its levels were not particularly high, which may be ascribed to the fact that smooth muscle cells in atherosclerotic lesions have a lower energy requirement and an appreciable proliferation rate, as compared for instance with cardiac myocytes. When the subjects were divided into two numerically equivalent age classes (60-72 years 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, cigarettes consumption, other clinical and anamnestic parameters or with the levels of adducts and 8-hydroxy-2'-deoxyguanosine measured in the nuclear DNA of the same samples. A previously unreported deletion of 5111 bp was additionally found in the mtDNA from a 45-year-old woman. The origin of this lesion seems to be compatible with the slipped mispairing model proposed for the 'common deletion'.
Bogliolo
M
M
Laboratory of Mutagenesis-CSTA, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Izzotti
A
A
De Flora
S
S
Carli
C
C
Abbondandolo
A
A
Degan
P
P
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001012:Aorta, Abdominal / Q000737:chemistry; D001161:Arteriosclerosis / Q000235:genetics*; D001482:Base Composition; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000302:isolation & purification; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D017384:Sequence Deletion / Q000235:genetics*; D012737:Sex Factors
D004272:DNA, Mitochondrial