Lindsey Merry L, Lange Richard A, Parsons Helen, Andrews Thomas, Aune Gregory J
Department of Physiology and Biophysics, San Antonio Cardiovascular Proteomics Center and Jackson Center for Heart Research, Mississippi Medical Center, Jackson, Mississippi;
Division of Cardiology, Department of Medicine, San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center San Antonio, San Antonio, Texas;
Am J Physiol Heart Circ Physiol. 2014 Nov 15;307(10):H1379-89. doi: 10.1152/ajpheart.00099.2014. Epub 2014 Sep 12.
Since the modern era of cancer chemotherapy that began in the mid-1940s, survival rates for children afflicted with cancer have steadily improved from 10% to current rates that approach 80% (60). Unfortunately, many long-term survivors of pediatric cancer develop chemotherapy-related health effects; 25% are afflicted with a severe or life-threatening medical condition, with cardiovascular disease being a primary risk (96). Childhood cancer survivors have markedly elevated incidences of stroke, congestive heart failure (CHF), coronary artery disease, and valvular disease (96). Their cardiac mortality is 8.2 times higher than expected (93). Anthracyclines are a key component of most curative chemotherapeutic regimens used in pediatric cancer, and approximately half of all childhood cancer patients are exposed to them (78). Numerous epidemiologic and observational studies have linked childhood anthracycline exposure to an increased risk of developing cardiomyopathy and CHF, often decades after treatment. The acute toxic effects of anthracyclines on cardiomyocytes are well described; however, myocardial tissue is comprised of additional resident cell types, and events occurring in the cardiomyocyte do not fully explain the pathological processes leading to late cardiomyopathy and CHF. This review will summarize the current literature regarding the cellular and molecular responses to anthracyclines, with an important emphasis on nonmyocyte cardiac cell types as well as those that mediate the myocardial injury response.
自20世纪40年代中期开始的现代癌症化疗时代以来，患癌症儿童的生存率已从10%稳步提高到目前接近80%的水平（60）。不幸的是，许多儿童癌症长期幸存者出现了化疗相关的健康问题；25%的人患有严重或危及生命的疾病，心血管疾病是主要风险（96）。儿童癌症幸存者中风、充血性心力衰竭（CHF）、冠状动脉疾病和瓣膜疾病的发病率显著升高（96）。他们的心脏死亡率比预期高8.2倍（93）。蒽环类药物是儿科癌症大多数治愈性化疗方案的关键组成部分，所有儿童癌症患者中约有一半接触过此类药物（78）。大量的流行病学和观察性研究表明，儿童接触蒽环类药物会增加患心肌病和CHF的风险，通常在治疗几十年后出现。蒽环类药物对心肌细胞的急性毒性作用已有充分描述；然而，心肌组织还包括其他驻留细胞类型，心肌细胞中发生的事件并不能完全解释导致晚期心肌病和CHF的病理过程。本综述将总结目前关于对蒽环类药物细胞和分子反应的文献，重点关注非心肌细胞类型以及介导心肌损伤反应的细胞类型。
