Michael E DeBakey Department of Surgery, Molecular Surgeon Research Center, Baylor College of Medicine, One Baylor Plaza, Mail Stop: BCM391, Houston, TX 77030, USA.
Expert Rev Mol Diagn. 2010 Mar;10(2):173-85. doi: 10.1586/erm.10.1.
Coronary artery disease, cerebrovascular disease, pulmonary artery hypertension and Alzheimer's disease all lead to substantial morbidity and mortality, and we currently lack effective treatments for these vascular diseases. Since the discovery, decades ago, that atherosclerotic lesions display clonal growth, atherosclerosis and other vascular diseases have been postulated to be neoplastic processes, arising through a series of critical somatic mutations. There is conflicting evidence supporting this but studies of DNA damage and mutagenesis, both genomic and mitochondrial, in atherosclerotic and vascular lesions, have yielded evidence that somatic mutations are involved in atherogenesis and vascular disease development. The roles of mitochondrial DNA damage, oxidative stress and signaling by members of the TGF-beta receptor family are implicated. With the increasing convenience and cost-effectiveness of genome sequencing, it is feasible to continue to seek specific genetic targets in the pathogenesis of these devastating diseases, with the hope of developing personalized genomic medicine in the future.
冠心病、脑血管病、肺动脉高压和阿尔茨海默病都导致了大量的发病率和死亡率，而我们目前缺乏对这些血管疾病的有效治疗方法。自从几十年前发现动脉粥样硬化病变表现出克隆性生长以来，动脉粥样硬化和其他血管疾病被假设为是肿瘤性过程，通过一系列关键的体细胞突变而产生。虽然有一些证据支持这一观点，但对动脉粥样硬化和血管病变中 DNA 损伤和突变的研究，无论是基因组还是线粒体，都表明体细胞突变参与了动脉粥样硬化形成和血管疾病的发展。线粒体 DNA 损伤、氧化应激以及 TGF-β 受体家族成员的信号转导都起作用。随着基因组测序的日益便利和成本效益的提高，继续寻找这些毁灭性疾病发病机制中的特定遗传靶点是可行的，未来有望开发出个性化的基因组医学。
