Selected aspects of cellular responses in heart failure.
Selected aspects of cellular responses in heart failure.
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心力衰竭细胞反应的选定方面。
DOI：
10.1097/fjc.0000000000000066
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发表时间：
2014
影响因子：
3
通讯作者：
Karliner,JoelS
中科院分区：
文献类型：
--
作者：
Karliner,JoelS
威廉·莎士比亚，《哈姆雷特》（1.5.166-7），《哈姆雷特》到霍雷肖。莎士比亚使用“哲学”一词来涵盖所有知识，过去的几十年无疑告诉我们，科学和医学的预测是危险的。哈姆雷特的话还表明，目前对确定拟议实验的未来影响的强调充满了错误。防止这种愚蠢行为的最好方法就是做好准备。本系列的综述文章重点关注心力衰竭细胞反应的选定方面，说明了过去几十年中出现的概念，这些概念可能在人类疾病中实际应用。正如最初设想的那样，这些概念可能被归类为科幻小说，但随着时间的推移，它们已经演变成科学“事实”。但事实和教条都是可塑的，毫无疑问，本系列文章中总结的许多概念将来都会被抛弃。问题是我们无法预测哪些会幸存。尽管如此，我们还是应该保持开放的心态，并希望已经种下适当的种子，并将其长成茂密的知识森林，经过修剪后，可用于治疗人类患者常见和新出现的心血管疾病。在第一篇文章中，Ye 和 Yeghiazarians 回顾了心脏祖细胞的当前知识状况，这些细胞已在实验和治疗上用于心脏细胞疗法。表格中详细介绍了这些细胞的特征，为读者（无论是新手还是专家）提供了这个年轻研究领域的广度和复杂性的概述。他们的综述总结了较早和最近的临床试验以及成功前景和未来方向，包括生物材料和 microRNA 技术的潜在作用。本综述引用的研究结果还强调了基础科学家和临床医生之间合作的重要性，以及在某些情况下，研究人员需要在建立坚实的知识基础之前抑制他们的热情。这个结论说明哈姆雷特是对的！没有什么地方比基因治疗领域的承诺和交付之间的差距更大了。在第二篇综述文章中，Hajjar 等人总结了通过使用腺相关病毒靶向 SERCA2a 来开发充血性心力衰竭基因治疗方法所取得的进展。这一概念利用了人类和动物模型心脏病理生理学基础研究中获得的信息，并说明了在使用新技术取得临床进展之前进行此类研究的必要性。在这篇综述中，确定了心力衰竭基因治疗的其他目标，以及基因治疗载体和递送系统及其陷阱。最后，综述总结了目前的临床试验结果。值得注意的是，基因疗法很可能与治疗心力衰竭的小型植入式心室辅助装置进行长期竞争。如上所述，无法预测哪种技术会更受欢迎。
William Shakespeare, Hamlet (1.5. 166–7), Hamlet to Horatio. Shakespeare uses the term “philosophy” to encompass all knowledge, and the past few decades have certainly taught us that prediction in science and medicine is perilous. Hamlet’s words also suggest that the current emphasis on identifying the future impact of proposed experiments is fraught with error. The best defense against such folly is the prepared mind. The review articles in this series, which focus on selected aspects of cellular responses in heart failure, illustrate the emergence of concepts during the past few decades with possible practical application for human disease. As originally conceived, these concepts might have been categorized as science fiction, but over time they have morphed into science “fact.” But facts and dogma are malleable, and no doubt many of the concepts summarized in this series of articles will be discarded in the future. The problem is that we cannot predict which ones will survive. Nevertheless, it behooves us to keep an open mind and to hope that the proper seeds have been planted and will grow into a thick forest of knowledge that, after pruning, can be used to treat both common and emerging cardiovascular disorders in human patients.In the first of these articles, Ye and Yeghiazarians review the current state of knowledge of cardiac progenitor cells that have been used for cardiac cell therapy both experimentally and therapeutically. The characteristics of these cells are detailed in tables, which provide the reader, both novice and expert, with an overview of the breadth and complexity of this young field of research. Their review summarizes both older and recent clinical trials and the prospects for success as well as future directions, including the potential roles of biomaterials and microRNA technology. The results of the studies cited in this review also emphasize the importance of collaboration between basic scientists and clinicians and the need, in some instances, for investigators to curb their enthusiasm before a solid base of knowledge is established. This conclusion shows that Hamlet had it right! Nowhere is the gap between promise and delivery greater than in the field of gene therapy. In the second review article, Hajjar et al summarize the progress that has been made in developing an approach to the gene therapy of congestive heart failure by targeting SERCA2a using an adeno-associated virus. This concept makes use of information gained in basic studies of cardiac pathophysiology in both humans and animal models and illustrates the need for such studies before clinical progress can be made using new technologies. In this review, other targets for gene therapy in heart failure are identified, as are gene therapy vectors and delivery systems and their pitfalls. Finally, the review summarizes the current results of clinical trials. It should be noted that gene therapy is likely to be in long-term competition with small implantable ventricular assist devices for the treatment of heart failure. Which technology will emerge as preferable is impossible to predict, as noted above.