Minamino Tohru, Komuro Issei
Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, Japan.
Front Biosci. 2008 Jan 1;13:2971-9. doi: 10.2741/2902.
Telomeres are DNA regions composed of TTAGGG repeats that are located at the ends of chromosomes. Specific proteins associate with the telomeres and form non-nucleosomal DNA-protein complexes that serve as protective caps for the chromosome ends. There is accumulating evidence that progressive telomere shortening is closely related to cardiovascular disease. For example, vascular cell senescence has been reported to occur in human atherosclerotic lesions and this change is associated with telomere shortening. Impairment of telomere integrity causes vascular dysfunction, which is prevented by the activation of telomerase. Mice with short telomeres develop hypertension and exhibit impaired neovascularization. Short telomeres have also been reported in the leukocytes of patients with cardiovascular disease or various cardiovascular risk factors. Although it remains unclear whether short telomeres directly cause cardiovascular disease, manipulation of telomere function is potentially an attractive strategy for the treatment of vascular senescence.
端粒是由TTAGGG重复序列组成的DNA区域,位于染色体末端。特定蛋白质与端粒结合,形成非核小体DNA-蛋白质复合物,作为染色体末端的保护帽。越来越多的证据表明,端粒的逐渐缩短与心血管疾病密切相关。例如,据报道,血管细胞衰老发生在人类动脉粥样硬化病变中,这种变化与端粒缩短有关。端粒完整性受损会导致血管功能障碍,而端粒酶的激活可预防这种情况。端粒短的小鼠会患高血压并表现出新血管生成受损。心血管疾病患者或各种心血管危险因素患者的白细胞中也有短端粒的报道。尽管尚不清楚短端粒是否直接导致心血管疾病,但操纵端粒功能可能是治疗血管衰老的一种有吸引力的策略。