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pmid:35837601

One-Week Dynamic Changes in Cardiac Proteomes After Cardiac Radioablation in Experimental Rat Model.

Byoung Hyuck Kim · Jin Woo Jung · Dohyun Han · Myung-Jin Cha · Ji Hyun Chang

Frontiers in cardiovascular medicine · 2022 doi:10.3389/fcvm.2022.898222

Paper

complete

Experiment

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Data

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One-Week Dynamic Changes in Cardiac Proteomes After Cardiac Radioablation in Experimental Rat Model.
doi
10.3389/fcvm.2022.898222
pmid
35837601
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Byoung Hyuck Kim
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Jin Woo Jung
[2]
Dohyun Han
[3]
Myung-Jin Cha
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Ji Hyun Chang
journal
Frontiers in cardiovascular medicine
year
2022
abstract
Background: 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. Methods: 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 via ProteomeXchange with identifier PXD030878. Results: 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. Conclusions: 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.
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At day 3, 200 proteins were differentially expressed after 25 Gy, of which 169 did not overlap with DEPs in control vs. 2 Gy (Figure 4C).
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After Cardiac Radioablation in Experimental Rat Model.
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4Detailed dose group comparison scheme after LC-MS/MS analysis. The differentially expressed prote
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1Overall experimental scheme of quantitative proteomic analysis.Click here for additional data file
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Complete file
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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.\nMethods: 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. 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