RNA sequencing reveal impact of radiation on cardiac tissues
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE255063 | GEO | 2025/03/19
REPOSITORIES: GEO
Similar Datasets
Project description:RNA sequencing reveal impact of radiation on cardiac tissues
| PRJNA1073450 | ENA
Project description:Low-LET radiation can cause cardiovascular dysfunctions at high-dose rates. For example, photons used in thoracic radiotherapy are known to cause acute cardiac tissue damage with elevated serum cardiac Troponin I level and long-term cardiac complications when delivered as fractionated exposures at high-dose rates. However, the effects of continuous low-dose rate radiation exposure on the heart, which simulate the space radiation environment, have not been well-studied. In this study, we aim to model low-LET space radiation-induced cardiovascular dysfunction using human induced pluripotent stem cell (iPSC)-derived engineered heart tissues (EHTs) exposed to protracted γ-ray irradiation. The investigation of pathophysiological changes in this model may provide insights and guide the development of countermeasures. As a proof-of-principle for the application of this model in drug development, we also tested the protective effect of a mitochondrial-specific antioxidant, MitoTempo, on irradiated EHTs.
2023-09-05 | GSE242108 | GEO
Project description:Radiation-induced Circulating microRNAs predict cardiac dysfunction after radiotherapy
| PRJNA934403 | ENA
Project description:Purpose: Studies during the past 9 years suggest that delivering radiation at dose rates exceeding 40 Gy/s, known as “FLASH” radiotherapy, enhances the therapeutic index of radiation therapy (RT) by decreasing normal tissue damage while maintaining tumor response compared to conventional (or standard) RT. This study demonstrates the cardioprotective benefits of FLASH proton RT (F-PRT) compared to standard (conventional) proton RT (S-PRT), as evidenced by reduced acute and chronic cardiac toxicities. Methods and Materials: Mice were imaged using cone beam computed tomography to precisely determine the heart’s apex as the beam isocenter. Irradiation was conducted utilizing a shoot-through technique with a 5mm collimator. Bulk RNA-sequencing was performed on non-irradiated (NR) samples, as well as apexes treated with F-PRT or S-PRT, at 2 weeks following a single 40 Gy dose. Inflammatory responses were assessed through multiplex cytokine/chemokine microbead assay and immunofluorescence analyses. Levels of perivascular fibrosis were quantified using Masson’s Trichrome and Picrosirius red staining. Additionally, cardiac tissue functionality was evaluated by 2D echocardiograms at 8 and 30 weeks post-PRT. Results: Radiation damage was specifically localized in the heart’s apex. RNA profiling of cardiac tissues treated with PRT revealed that S-PRT induced unique pathways associated with DNA damage response, induction of tumor necrosis factor superfamily and inflammatory response, while F-PRT primarily affected cytoplasmic translation, mitochondrion organization and ATP synthesis. Notably, F-PRT led to a milder inflammatory response, accompanied by significantly attenuated changes in TGF-1 and SMA levels. Critically, F-PRT decreased collagen deposition, and better preserved cardiac functionality compared to S-PRT. Conclusions: This study demonstrated that F-PRT reduces the induction of an inflammatory environment with lower expression of inflammatory cytokines and profibrotic factors. Importantly, the results indicate that F-PRT better preserves cardiac functionality, as confirmed by echocardiography analysis, while also mitigating the development of long-term fibrosis.
2024-07-11 | GSE261367 | GEO
Project description:Here, we present a whole-genome survey of the murine transcriptomic response to physiologically-relevant radiation doses, 2 and 8 Gy. There are 18 distinct biological samples here. Mice were exposed to ionizing radiation (Cesium-138 source) and whole blood was collected by cardiac puncture 6 hours post treatment. Doses were 0 (7 samples), 2 (5 samples), and 8 (6 samples) gy.
2012-05-31 | E-GEOD-33172 | biostudies-arrayexpress
Project description:C57BL6/J mice were treated with anti-PD-1 for 2 or 4 weeks, or with isotype control antibody. In echocardiography, cardiac dysfunction was seen both after 2 and 4 weeks, with decreased ejection fraction and left ventricular dilation. Bulk RNA sequencing of the hearts after treatment was performed to identify the mechanisms of anti-PD-1-induced cardiac dysfunction.
2022-12-03 | E-MTAB-12388 | biostudies-arrayexpress
Project description:Metabolic reprogramming is critical in the onset of pressure overload-induced cardiac remodeling. Our study reveals that proline dehydrogenase (PRODH), the key enzyme in proline metabolism, reprograms cardiomyocyte metabolism to protect against cardiac remodeling. We induced cardiac remodeling using transverse aortic constriction (TAC) in both cardiac-specific PRODH knockout and overexpression mice. Our results indicate that PRODH expression is suppressed post-TAC. Cardiac-specific PRODH knockout mice exhibited worsened cardiac dysfunction, while mice with PRODH overexpression demonstrated a protective effect. Additionally, we simulated cardiomyocyte hypertrophy in vitro using neonatal rat ventricular myocytes treated with phenylephrine. Through RNA sequencing, metabolomics, and metabolic flux analysis, we elucidated that PRODH overexpression in cardiomyocytes redirects proline catabolism to replenish tricarboxylic acid (TCA) cycle intermediates, enhance energy production, and restore glutathione redox balance. In summary, our findings suggest PRODH as a modulator of cardiac bioenergetics and redox homeostasis duing cardiac remodeling induced by pressure overload. This highlights the potential of PRODH as a therapeutic target for cardiac remodeling.
2025-02-28 | GSE260465 | GEO
Project description:Cardiac fibroblasts were isolated from 3-month old C57BL/6 mice. RNA was prepared from quiescent, serum-starved cardiac fibroblasts in passage 15. A total number of 118654 tags was sequenced. After removal of duplicate ditags and linker-derived sequences 110169 tags remained. This GEO Series was created by the GEO staff as part of a cleanup effort to ensure that all GEO Samples are included within a Series entry.
2010-12-01 | E-GEOD-25757 | biostudies-arrayexpress
Project description:An intrinsic property of the heart is an ability to rapidly and coordinately adjust flux through metabolic pathways in response to physiologic stimuli (termed metabolic flexibility). Cardiac metabolism also fluctuates across the 24-hr day, in association with diurnal sleep-wake and fasting-feeding cycles. Although loss of metabolic flexibility has been proposed to play a causal role in the pathogenesis of cardiac disease, it is currently unknown whether day-night variations in cardiac metabolism are altered during disease states. Here, we tested the hypothesis that diet-induced obesity disrupts cardiac “diurnal metabolic flexibility”, which is normalized by time-of-day-restricted feeding. Chronic high fat feeding (20-wk) induced obesity in mice, abolished diurnal rhythms in whole body metabolic flexibility, and increased markers of adverse cardiac remodeling (hypertrophy, fibrosis, and steatosis). RNAseq analysis revealed that 24-hr rhythms in the cardiac transcriptome were dramatically altered during obesity; only 22% of rhythmic transcripts in control hearts were unaffected by obesity. However, day-night differences in cardiac substrate oxidation were essentially identical in control and high fat fed mice. In contrast, day-night differences in both cardiac triglyceride synthesis and lipidome were abolished during obesity. Next, a subset of obese mice (induced by 18-wks ad libitum high fat feeding) were allowed access to the high fat diet only during the 12-hr dark (active) phase, for a 2-wk period. Dark phase restricted feeding partially restored whole body metabolic flexibility, as well as day-night differences in cardiac triglyceride synthesis and lipidome. Moreover, this intervention partially reversed adverse cardiac remodeling in obese mice. Collectively, these studies reveal diurnal metabolic inflexibility of the heart during obesity specifically for non-oxidative lipid metabolism (but not for substrate oxidation), and that restricting food intake to the active period partially reverses obesity-induced cardiac lipid metabolism abnormalities and adverse remodeling of the heart.
2021-04-09 | GSE171710 | GEO
Project description:The contribution of radiotherapy, per se, in late cardiotoxicity remains controversial. An experimental model was developed, in which rat hearts were exposed to a range of ionizing radiation doses, to clarify its impact on the development of early cardiac dysfunction. Rat’s hearts were exposed to daily doses of 0.04, 0.3 and 1.2 Gy, for 23 days, achieving cumulative doses of 0.92, 6.9 and 27.6 Gy, respectively. Myocardial deformation, assessed by global longitudinal strain, was impaired (a relative percentage reduction of > 15% from baseline) in a dose-dependent manner. Moreover, by scanning electron microscopy, the microvascular density in the cardiac apex was significantly decreased exclusively at 27.6 Gy dosage. Prior to GLS impairment detection, several tools (qRT-PCR, mass spectrometry and western blot) were used to assess cardiac tissue remodeling. The number/expression of several genes, proteins and KEGG pathways, related to inflammation, fibrosis and cardiac muscle contraction, were found to be differently expressed in the cardiac tissue, according to the cumulative dose. Subclinical cardiac dysfunction occurred in a dose-dependent manner as detected by cardiac tissue remodeling, a predictor of the severity of global longitudinal strain impairment. Moreover, there is no dose threshold below which no myocardial deformation impairment was detected. These findings may contribute to i) develop new markers and explore non-invasive magnetic resonance imaging to assess cardiac tissue remodeling as an early predictor of cardiac dysfunction; ii) improve radiation-based diagnostic and therapeutic cardiac procedures; iii) highlight the need for personalized clinical approaches.
2022-09-08 | PXD033194 | Pride