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

doi:10.3389/fcvm.2022.898222

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

Front Cardiovasc Med. 2022 Jun 28:9:898222. doi: 10.3389/fcvm.2022.898222. eCollection 2022.

Authors

Byoung Hyuck Kim^{1

2}, Jin Woo Jung³, Dohyun Han^{3

4}, Myung-Jin Cha⁵, Ji Hyun Chang²

Affiliations

¹ Department of Radiation Oncology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, South Korea.
² Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, South Korea.
³ Proteomics Core Facility, Transdisciplinary Research and Collaboration, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.
⁴ Transdisciplinary Department of Medicine and Advanced Technology, Seoul National University Hospital, Seoul, South Korea.
⁵ Division of Cardiology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

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.

Keywords: antiarrhythmic effects; cardiac conduction system; proteomics; radioablation; rats (all MESH terms).