Multiple skeletal muscle mitochondrial DNA deletions in patients with unilateral peripheral arterial disease.
Peripheral arterial disease (PAD) is associated with metabolic derangements and accumulation of the common 4977 bp mitochondrial DNA (mtDNA) deletion mutation. The current study was undertaken to test the hypothesis that PAD is associated with multiple mtDNA deletions. Gastrocnemius biopsies were obtained from nine patients with unilateral PAD. DNA extracted from the biopsies was analyzed for mtDNA deletions using a primer-shift PCR strategy. Multiple primers and strict, prospective criteria were used to identify deletions. PAD was associated with multiple mtDNA deletions (average of 8.2 distinct deletions in muscle from the hemodynamically affected limb). mtDNA injury was present in both the worse- and less-affected limbs of the unilateral PAD patients, and the estimated degree of mtDNA injury was strongly correlated in the two limbs on an intra-subject basis. The 4977 bp deletion was frequently identified, but was not always the deletion of highest frequency in individual samples. The estimated relative frequency of the 4977 bp deletion was correlated with the overall mtDNA injury in the biopsies. In summary, PAD is associated with mtDNA injury as reflected by multiple deletion mutations. As the mutations are not limited to the ischemic limb in unilateral patients, they are unlikely to contribute to the pathophysiology of claudication.
Brass
E P
EP
Department of Medicine, Harbor-UCLA Medical Center, Torrance 90509, USA.
Wang
H
H
Hiatt
W R
WR
D000368:Aged; D017931:DNA Primers / Q000737:chemistry; D004272:DNA, Mitochondrial / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D007383:Intermittent Claudication / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D007511:Ischemia / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000235:genetics*; D018482:Muscle, Skeletal / Q000473:pathology*; D016491:Peripheral Vascular Diseases / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012720:Severity of Illness Index
D017931:DNA Primers; D004272:DNA, Mitochondrial