Figure - available from: Naunyn-Schmiedeberg's Archives of Pharmacology
This content is subject to copyright. Terms and conditions apply.
Adriamycin (ADR) treatment decreased cTnI expression in cardiomyocytes. a The mice were treated as indicated, and the heart tissues were harvested after echocardiographic analysis. The expression of the cTnI and GAPDH was measured using Western blotting and the normalized expression intensity of cTnI is shown. Each experiment was performed three times. Data are expressed as mean ± SD (n = 4). *p < 0.05. b, c H9c2 and AC16 cells were treated with ADR (1 μM) for 24 h. The expression of the cTnI and GAPDH were measured using Western blotting and the normalized expression intensity of cTnI is shown. Each experiment was performed three times. Data are expressed as mean ± SD (n = 3). *p < 0.05, **p < 0.01. d Effect of ADR on the degradation rate of cTnI protein in H9c2 cells. Cells were lysed at different time points (0, 1, 3, 6, 12, 24 h). e ADR accelerated the degradation of cTnI in AC16 cells. The cTnI protein half-life was observed shorter (12 h) under ADR treatment than CHX only (longer than 24 h)
Source publication
Although anthracyclines improve the long-term survival rate of patients with cancer, severe and irreversible myocardial damage limits their clinical application. Amino acid (AA) metabolism in cardiomyocytes can be altered under pathological conditions. Therefore, exploring the AA metabolic signature in anthracycline-induced cardiotoxicity (AIC) is...
Similar publications
The egg yolk of the goose is rich in lipids, proteins and minerals, which is the main source of nutrition during the goose embryogenesis. Actually, the magnitude and variety of nutrients in yolk are dynamically changed to satisfy the nutritional requirements of different growth and development periods. The yolk sac membrane (YSM) plays a role in me...
Citations
... The findings revealed that metabolic disorders, including those related to the tricarboxylic acid cycle, glutathione metabolism, glycolysis, glycerophospholipid metabolism, and fatty acid metabolism, contribute to the development of heart failure. Anthracyclines can affect aminoacyl-transfer RNA biosynthesis and interfere with glutamate, aspartic acid, and alanine metabolism by disrupting amino acid metabolism in the cardiotoxicity model [106]. In a clinical study, Asnani et al. [107] evaluated the role of intermediate metabolism in 38 breast cancer patients treated with anthracyclines and trastuzumab. ...
Opinion statement
Cardio-oncology is an emerging interdisciplinary field dedicated to the early detection and treatment of adverse cardiovascular events associated with anticancer treatment, and current clinical management of anticancer-treatment-related cardiovascular toxicity (CTR-CVT) remains limited by a lack of detailed phenotypic data. However, the promise of diagnosing CTR-CVT using deep phenotyping has emerged with the development of precision medicine, particularly the use of omics-based methodologies to discover sensitive biomarkers of the disease. In the future, combining information produced by a variety of omics methodologies could expand the clinical practice of cardio-oncology. In this review, we demonstrate how omics approaches can improve our comprehension of CTR-CVT deep phenotyping, discuss the positive and negative aspects of available omics approaches for CTR-CVT diagnosis, and outline how to integrate multiple sets of omics data into individualized monitoring and treatment. This will offer a reliable technical route for lowering cardiovascular morbidity and mortality in cancer patients and survivors.
Introduction
Despite the well-established efficacy of thiazolidinediones (TZDs), including pioglitazone and rosiglitazone, in type II diabetes management, their potential contribution to heart failure risk remains a significant area of uncertainty. This incomplete understanding, which persists despite decades of clinical use of TZDs, has generated ongoing controversy and unanswered questions regarding their safety profiles, ultimately limiting their broader clinical application.
Objective and Methods
This study presented a multi-omics approach, integrating toxicoproteomics and toxicometabolomics data with the goal of uncovering novel mechanistic insights into TZD cardiotoxicity and identifying molecular signatures predictive of side effect progression.
Results
Network analysis of proteo-metabolomic data revealed a distinct fingerprint of disrupted biochemical pathways, which were primarily related to energy metabolism. Downregulation of oxidative phosphorylation and fatty acid synthesis was coupled with increased activity in anaerobic glycolysis, the pentose phosphate pathway, and amino acid and purine metabolism. This suggests a potential metabolic shift in AC16 cells from fatty acid oxidation towards anaerobic glycolysis, potentially contributing to observed cardiotoxicity. Additionally, the study identified a marked disruption in the glutathione system, indicating an imbalanced redox state triggered by TZD exposure. Importantly, our analysis identified key molecular signatures across omics datasets, including prominent signatures of amino acids like L-ornithine, L-tyrosine and glutamine, which are established heart failure biomarkers, supporting their potential use for the early prediction of cardiotoxicity progression.
Conclusion
By uncovering a novel mechanistic explanation for TZD cardiotoxicity, this study simultaneously illuminates potential therapeutic interventions, opening avenues for future research to improve the safety profile of TZD agents.
