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

Abstract

BackgroundRecently, 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.MethodsIn 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.ResultsFunctional 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.Conclusions25 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.

Stereotactic Arrhythmia Radioablation (STAR): A Multidisciplinary Narrative Minireview of Preclinical Studies

“…Studies on the biological effect of STAR showed: i) cell apoptosis (by detecting cleaved caspase-3 as a marker) in the irradiated volumes three months after treatment but not after six months (18,24), ii) increased expression of connexin 43 (10,11,19,27) and a variety of other proteins (28) and iii) increased gap junctions (11). Moreover, other studies reported: i) clear histological evidence of STAR effect on the target area, found by the loss of myocyte architecture and increased fibrin, vacuoles and calcification (12), and ii) fibrosis in the same area, detected by loss of the smooth cellular organization usually seen in normal AV nodes, extensive fibrin deposition and marked elastosis, but not in the surrounding tissues (21,24,26,30).…”

Heavy Ion Irradiation Reduces Vulnerability to Atrial Tachyarrhythmias ― Gap Junction and Sympathetic Neural Remodeling ―

“…34 Hierarchical clustering of the cardiac proteome within 1 week after 25 Gy of X-rays using rats showed significant expression of actin filament proteins. 35 As a response to radiation-induced hyperacute oxidative stress, we can focus on genes and immune activity related to the process of early-stage cardiac remodeling for radiation.…”

Molecular Mechanism of Male Sterility Induced by 60Co γ-Rays on Plutella xylostella (Linnaeus)

“…Compared with traditional differential electrophoresis, proteomics technology based on mass spectrometry has obvious advantages in sensitivity, detection range, high throughput, accuracy, and automation [18]. Therefore, more and more research teams have begun to use proteomics technology for irradiation related research [19,20]. Although the use of SIT to control Lepidoptera pests is theoretically feasible, the mechanism of damage to the reproductive system of P. xylostella via irradiation and the mechanism of how the reproductive system resists different doses of irradiation are still unclear.…”