Kim Byoung Hyuck, Jung Jin Woo, Han Dohyun, Cha Myung-Jin, Chang Ji Hyun
Department of Radiation Oncology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, South Korea.
Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, South Korea.
Front Cardiovasc Med. 2022 Jun 28;9:898222. doi: 10.3389/fcvm.2022.898222. eCollection 2022.
Recently, stereotactic ablative radiotherapy (SABR) has been adopted to non-invasively treat catheter ablation-refractory ventricular tachycardia (VT). VT episodes have been dramatically reduced after SABR, within weeks; however the underlying mechanisms of these clinical effects and potential mediators of early anti-arrhythmic effect remain unclear.
In this study, cardiac tissue was harvested from non-irradiated control (0 Gy), conventional irradiated control (2 Gy), and radioablative test (25 Gy) rat groups after 3 and 7 days of irradiation. The samples were proteomically analyzed to identify the differentially expressed proteins (DEP) between different groups. Validation experiments were performed similar to validation in profiling where Data independent acquisition and parallel reaction monitoring methods were used. Data are available ProteomeXchange with identifier PXD030878.
Functional enrichment analysis of 25 Gy sample showed that among the downregulated proteins, "intracellular signal transduction" and "cell to cell adhesion" proteins were significantly affected at day 3 while "Ras protein signal transduction," "GTPase regulation," and "actin filament-based process" proteins were majorly affected at day 7. GO analysis demonstrated that most of the upregulated proteins belonged to the classes "cellular stress response," "endomembranal organization," or "endoplasmic reticulum stress response" at day 3. At day 7, 42 proteins, mainly associated with response to drug, organic substance, or radiation, were specifically upregulated in 25 Gy. DEP analysis of cardiac conduction showed Ryr2 and Cav1 upregulation and Cacna2d2, Gja3, Scnb2, and Kcnn3 downregulation in the 25 Gy group compared to 0 Gy. In validation experiments, four proteins (Gsta1, Myot, Ephx1, and Capg) were repeatedly detected with 25 Gy-specific patterns at day 7.
25 Gy single fractional irradiation induces considerable cardiac proteome changes within the first 7 days, distinct from 2 Gy. Several candidate proteins displayed 25 Gy-specific changes and were related to oxidative stress-induced innate response or cardiac remodeling processes. Future studies should explore the specific role of these proteins upon cardiac radioablation.
最近，立体定向消融放疗（SABR）已被用于无创治疗导管消融难治性室性心动过速（VT）。SABR后数周内VT发作显著减少；然而，这些临床效果的潜在机制以及早期抗心律失常作用的潜在介质仍不清楚。
在本研究中，在照射3天和7天后，从未照射对照（0 Gy）、传统照射对照（2 Gy）和放射消融试验（25 Gy）大鼠组采集心脏组织。对样本进行蛋白质组学分析，以鉴定不同组之间的差异表达蛋白（DEP）。验证实验与分析中的验证类似，使用了数据非依赖采集和平行反应监测方法。数据可在ProteomeXchange上获取，标识符为PXD030878。
对25 Gy样本的功能富集分析表明，在下调的蛋白质中，“细胞内信号转导”和“细胞间粘附”蛋白在第3天受到显著影响，而“Ras蛋白信号转导”、“GTP酶调节”和“基于肌动蛋白丝的过程”蛋白在第7天受到主要影响。基因本体（GO）分析表明，在第3天，大多数上调的蛋白质属于“细胞应激反应”、“内膜组织”或“内质网应激反应”类别。在第7天，25 Gy组中42种主要与药物、有机物质或辐射反应相关的蛋白质特异性上调。与0 Gy相比，25 Gy组心脏传导的DEP分析显示Ryr2和Cav1上调，Cacna2d2、Gja3、Scnb2和Kcnn3下调。在验证实验中，在第7天重复检测到4种蛋白质（Gsta1、Myot、Ephx1和Capg）具有25 Gy特异性模式。
25 Gy单次分割照射在最初7天内可引起相当大的心脏蛋白质组变化，与2 Gy不同。几种候选蛋白表现出25 Gy特异性变化，与氧化应激诱导的先天性反应或心脏重塑过程有关。未来的研究应探索这些蛋白质在心脏放射消融中的具体作用。
