Minamino Tohru, Komuro Issei
Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Curr Opin Lipidol. 2002 Oct;13(5):537-43. doi: 10.1097/00041433-200210000-00010.
Telomeres consist of repeats of G-rich sequence at the end of chromosomes. These DNA repeats are synthesized by enzymatic activity associated with an RNA protein complex called telomerase. In most somatic cells, telomerase activity is insufficient, and telomere length decreases with increasing cell division, resulting in an irreversible cell growth arrest, termed cellular senescence. Cellular senescence is associated with an array of phenotypic changes suggestive of aging. Until recently, cellular senescence has largely been studied as an in-vitro phenomenon; however, there is accumulating evidence that indicates a critical role of telomere function in the pathogenesis of human atherosclerosis. This review attempts to summarize recent work in vascular biology that supports the "telomere hypothesis". We discuss the possible relevance of telomere function to vascular aging and the therapeutic potential of telomere manipulation.
It has been reported that many of the changes in senescent vascular cell behavior are consistent with known changes seen in age-related vascular diseases. Introduction of telomere malfunction has been shown to lead to endothelial dysfunction that promotes atherogenesis, whereas telomere lengthening extends cell lifespan and protects against endothelial dysfunction associated with senescence. Indeed, recent studies have demonstrated that telomere attrition and cellular senescence occur in the blood vessels and are associated with human atherosclerosis.
Recent findings suggest that vascular cell senescence induced by telomere shortening may contribute to atherogenesis and may provide insights into a novel treatment of antisenescence to prevent atherosclerosis.
端粒由染色体末端富含G的序列重复组成。这些DNA重复序列由与一种名为端粒酶的RNA蛋白复合物相关的酶活性合成。在大多数体细胞中，端粒酶活性不足，端粒长度随细胞分裂增加而缩短，导致不可逆的细胞生长停滞，即细胞衰老。细胞衰老与一系列提示衰老的表型变化相关。直到最近，细胞衰老在很大程度上一直作为一种体外现象进行研究；然而，越来越多的证据表明端粒功能在人类动脉粥样硬化发病机制中起关键作用。本综述试图总结血管生物学领域支持“端粒假说”的近期研究工作。我们讨论端粒功能与血管衰老的可能相关性以及端粒操纵的治疗潜力。
据报道，衰老血管细胞行为的许多变化与年龄相关血管疾病中已知的变化一致。端粒功能异常的引入已被证明会导致促进动脉粥样硬化发生的内皮功能障碍，而端粒延长可延长细胞寿命并防止与衰老相关的内皮功能障碍。事实上，近期研究表明端粒磨损和细胞衰老发生在血管中，并与人类动脉粥样硬化相关。
近期发现表明，端粒缩短诱导的血管细胞衰老可能促进动脉粥样硬化的发生，并可能为预防动脉粥样硬化的抗衰老新疗法提供思路。
