title: Detection of mtDNA with 4977 bp deletion in blood cells and atherosclerotic lesions of patients with coronary artery disease.
abstract: Recent evidence suggests that somatic mutations in nuclear and mitochondrial DNA accumulated during aging, may significantly contribute to the pathogenesis of chronic-degenerative illness such as coronary artery disease (CAD). Mitochondrial DNA with 4977 bp deletion mutation (mtDNA4977) is a common type of mtDNA alteration in humans. However, little attempt has been made to detect the presence of mtDNA4977 deletion in cells and tissues of cardiovascular patients. This study investigated the presence of mtDNA4977 in blood samples of 65 cardiovascular patients and 23 atherosclerotic plaques of human coronaries with severe atherosclerosis. Moreover, the presence of the deletion has been investigated in blood cells from 22 healthy age-matched subjects. The detection of mtDNA4977 has been performed by using a nested polymerase chain reaction (PCR) protocol and normalized to wild-type mtDNA. A significant higher incidence of mtDNA4977 was observed in CAD patients with respect to healthy subjects (26.2% versus 4.5%; P=0.03). Furthermore, the relative amount of the deletion was significantly higher in the patients compared to the control group (P=0.02). The mtDNA4977 was detected in 17 of the 65 patients blood samples (26.2%) and deletion levels ranged from 0.18 to 0.46% of the total mtDNA (mean: 0.34+/-0.02%). For what concerns atherosclerotic lesions, 5 patients (21.7%) showed the deletion ranging from 0.13 to 0.45% of the total mtDNA (mean: 0.35+/-0.06%). In both samples from patients, the incidence and the relative amount of mtDNA4977 was not significantly influenced by atherogenic risk factors and clinical parameters. The obtained results may suggest that the increase of oxidative stress in cardiovascular disease may be responsible for the accumulation of mtDNA damage in coronary artery disease patients.
authors.affiliation: CNR, Institute of Clinical Physiology, G. Pasquinucci Hospital, Massa, Italy. botto@ifc.cnr.it
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Botto
authors.forename: Sergio
authors.initials: S
authors.lastname: Berti
authors.forename: Samantha
authors.initials: S
authors.lastname: Manfredi
authors.forename: Anees
authors.initials: A
authors.lastname: Al-Jabri
authors.forename: Chiara
authors.initials: C
authors.lastname: Federici
authors.forename: Aldo
authors.initials: A
authors.lastname: Clerico
authors.forename: Enrica
authors.initials: E
authors.lastname: Ciofini
authors.forename: Andrea
authors.initials: A
authors.lastname: Biagini
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Andreassi
mesh_terms: D001483:Base Sequence; D003324:Coronary Artery Disease / Q000235:genetics* / Q000378:metabolism; D004272:DNA, Mitochondrial; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics*; D012307:Risk Factors; D017384:Sequence Deletion
chemical_list: D004272:DNA, Mitochondrial