From the Molecular Cardiology Unit, Whitaker Cardiovascular Institute, Boston University School of Medicine, MA.
Circ Res. 2018 Feb 2;122(3):523-532. doi: 10.1161/CIRCRESAHA.117.312115.
Increasing evidence shows that conventional cardiovascular risk factors are incompletely predictive of cardiovascular disease, particularly in elderly individuals, suggesting that there may still be unidentified causal risk factors. Although the accumulation of somatic DNA mutations is a hallmark of aging, its relevance in cardiovascular disease or other age-related conditions has been, with the exception of cancer, largely unexplored. Here, we review recent clinical and preclinical studies that have identified acquired mutations in hematopoietic stem cells and subsequent clonal hematopoiesis as a new cardiovascular risk factor and a potential major driver of atherosclerosis. Understanding the mechanisms underlying the connection between somatic mutation-driven clonal hematopoiesis and cardiovascular disease will be highly relevant in the context of personalized medicine, as it may provide key information for the design of diagnostic, preventive, or therapeutic strategies tailored to the effects of specific somatic mutations.
越来越多的证据表明，传统的心血管危险因素不能完全预测心血管疾病，尤其是在老年人中，这表明可能仍然存在未被识别的因果危险因素。尽管体细胞 DNA 突变的积累是衰老的一个标志，但除了癌症之外，其在心血管疾病或其他与年龄相关的疾病中的相关性在很大程度上尚未被探索。在这里，我们回顾了最近的临床和临床前研究，这些研究已经确定了造血干细胞中的获得性突变和随后的克隆性造血作为一种新的心血管危险因素，也是动脉粥样硬化的一个潜在主要驱动因素。了解体细胞突变驱动的克隆性造血与心血管疾病之间的联系的机制在个性化医学的背景下将是非常重要的，因为它可能为设计针对特定体细胞突变影响的诊断、预防或治疗策略提供关键信息。
