Detection of mtDNA with 4977 bp deletion in blood cells and atherosclerotic lesions of patients with coronary artery disease
Detection of mtDNA with 4977 bp deletion in blood cells and atherosclerotic lesions of patients with coronary artery disease
复制标题
DOI：
10.1016/j.mrfmmm.2004.10.003
复制
发表时间：
2005-02-15
影响因子：
2.3
通讯作者：
Andreassi, MG
中科院分区：
文献类型：
--
作者：
Botto, N;Berti, S;Andreassi, MG
最近的证据表明，衰老过程中积累的核和线粒体 DNA 的体细胞突变可能会显着促进冠状动脉疾病 (CAD) 等慢性退行性疾病的发病机制。具有 4977 bp 缺失突变的线粒体 DNA (mtDNA 4917) 是人类 mtDNA 改变的常见类型。然而，很少有人尝试检测心血管患者细胞和组织中mtDNA 4171缺失的存在。本研究调查了65名心血管患者的血液样本和23个患有严重动脉粥样硬化的人类冠状动脉粥样硬化斑块中mtDNA 4977的存在。此外，还对 22 名年龄匹配的健康受试者的血细胞中是否存在缺失进行了研究。通过使用巢式聚合酶链式反应 (PCR) 方案进行了 mtDNA 1977 的检测，并将其归一化为野生型 mtDNA。与健康受试者相比，在 CAD 患者中观察到 mtDNA 4977 的发生率显着较高（26.2% 对比 4.5%；P = 0.03）。此外，与对照组相比，患者的相对缺失量显着更高（P = 0.02）。 65 名患者血液样本中有 17 名 (26.2%) 检测到 mtDNA (4977)，缺失水平范围为总 mtDNA 的 0.18% 至 0.46%（平均值：0.34 +/- 0.02%）。对于动脉粥样硬化病变，5 名患者 (21.7%) 的缺失范围为总 mtDNA 的 0.13% 至 0.45%（平均值：0.35 +/- 0.06%）。在这两个患者样本中，mtDNA (4977) 的发生率和相对量并未受到致动脉粥样硬化危险因素和临床参数的显着影响。所获得的结果可能表明，心血管疾病中氧化应激的增加可能是导致冠心病患者 mtDNA 损伤累积的原因。(C) 2004 Elsevier B.V. 保留所有权利。
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 (mtDNA 4917) is a common type of mtDNA alteration in humans. However, little attempt has been made to detect the presence of mtDNA 4171 deletion in cells and tissues of cardiovascular patients.This study investigated the presence of mtDNA 4977 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 mtDNA 1977 has been performed by using a nested polymerase chain reaction (PCR) protocol and normalized to wild-type mtDNA.A significant higher incidence of mtDNA 4977 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 mtDNA(4977) 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 mtDNA(4977) 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 a(cumulation of mtDNA damage in coronary artery disease patients. (C) 2004 Elsevier B.V. All rights reserved.