Innovation and Discovery in Cardiovascular Biology.
Innovation and Discovery in Cardiovascular Biology.
复制标题
心血管生物学的创新与发现。
DOI：
10.1021/acsptsci.9b00077
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发表时间：
2019
影响因子：
--
通讯作者：
Caron,KathleenM
中科院分区：
文献类型：
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作者：
Caron,KathleenM
心血管生物学的创新和发现。尽管心血管疾病的检测和治疗取得了巨大进展，但作为一个群体，这些疾病仍然是全球死亡的头号原因，2016年约有1790万人死亡，占全球死亡人数的近三分之一。1特发性和顽固性高血压仍然是心血管疾病和中风的重要潜在起源，但血压调节功能障碍的遗传，环境和病理生理基础仍然不清楚。大规模的临床研究在揭示与心血管疾病相关的常见预测生物标志物或遗传变异方面取得了一些进展，因此，对高危人群的临床护理和管理在生命的早期就发生了。然而，我们的治疗武库并没有扩大到使我们能够实现个性化或从诊所到床边的医疗愿景。此外，在临床研究和全基因组关联研究中仍然存在对成年男性的广泛性别偏见，从而破坏了一般人群的推定诊断和治疗的最终成功。2因此，本期《药理学与转化科学》杂志重点关注与心血管疾病广泛相关领域的主要研究发现。我们特别征集使用创新技术方法和跨学科方法来阐明心血管病理生理学基础机制途径的提交材料。为了与该杂志的范围保持一致，我们很高兴收到专注于治疗策略和目标的提交材料。总的来说，这期关于心血管生物学创新和发现的特刊成功地整合了综述和主要研究文章，为新的诊断和治疗铺平了道路，并提高了对世界上最常见和最致命疾病的综合生理学的理解。两篇独立的文章集中在揭示与心功能障碍相关的新分子途径。缺血事件后心肌细胞的不可逆死亡是通过凋亡和坏死介导的，但最近的研究表明，坏死可能是一个可逆的事件。因此，Cheng等人3在人类肌肉细胞中使用全基因组RNAi筛选来鉴定钙诱导坏死中涉及的关键途径。他们发现了多种分子途径，包括几种可药用的酶，它们可以增强或抑制心肌细胞坏死，从而为心肌缺血提供了丰富的临床相关靶点数据集。Zhang et al. 4通过进行一项旨在发现化疗患者心脏毒性更好预测标志物的小规模临床研究，解决了化疗后心脏毒性和心力衰竭的复杂问题。使用纳米阱分级分离和血浆质谱，该小组能够富集组织蛋白酶B切割产生的血浆肽。他们发现了等离子体
Innovations and Discovery in Cardiovascular Biology. Despite tremendous advances in the detection and treatment of cardiovascular diseases, as a group these pathologies remain the number one cause of global death, accounting for approximately 17.9 million deaths in 2016; nearly one-third of all deaths worldwide. 1 Idiopathic and resistant hypertension remain significant underlying origins of cardiovascular disease and stroke, and yet the genetic, environmental, and pathophysiological underpinnings of dysfunctional blood pressure regulation remain murky. Large-scale clinical studies have made some progress toward revealing common predictive biomarkers or genetic variants associated with cardiovascular disease, so that clinical care and management of at-risk individuals is occurring earlier in life. However, our therapeutic arsenals have not expanded in a way that enables us to achieve our vision of personalized or bench-to-bedside medicine. In addition, there remains broad sex bias toward adult males in clinical studies and genome-wide association studies, thereby undermining the ultimate success of putative diagnostics and therapeutics for the general population. 2 Therefore, we focus this issue of Pharmacology and Translational Science on the publication of primary research discoveries in areas broadly related to cardiovascular disease. We specifically solicited submissions that used innovative technological approaches and interdisciplinary methodologies to elucidate mechanistic pathways underlying cardiovascular pathophysiology. In keeping with the scope of the journal, we were excited to receive submissions that focus on therapeutic strategies and targets. Collectively, this special issue on Innovations and Discovery in Cardiovascular Biology has been successful in coalescing reviews and primary research articles that pave the way toward new diagnostics and therapeutics as well as an improved understanding of the integrative physiology that underlies the world, s most common and deadly disease.Two separate articles are focused on revealing novel molecular pathways associated with cardiac dysfunction. The irreversible death of cardiomyocytes following an ischemic event is mediated through both apoptosis and necrosis, but recent studies suggest that necrosis may be a reversible event. Therefore, Cheng et al. 3 used a genome-wide RNAi screen in human muscle cells to identify key pathways involved in calcium-induced necrosis. They discovered multiple molecular pathways, encompassing several druggable enzymes, that either enhance or inhibit cardiomyocyte necrosis, thereby offering a rich data set of clinically relevant targets for cardiac ischemia. Zhang et al. 4 tackled the complex problem of cardiotoxicity and cardiac failure following chemotherapy by performing a small-scale clinical study aimed at discovering better predictive markers of cardiotoxicity in patients treated with chemotherapy. Using nanotrap fractionation and mass spectometry of plasma, the group was able to enrich for plasma peptides produced by cathepsin B cleavage. They discovered a plasma