Metabolites
Chamber–Specific Molecular Profiling of Doxorubicin-Induced Cardiotoxicity via Integrated Multi-Omics Analysis
By Jian Zhang, Yue Sun, Xiaozhen He and 3 others.
Abstract
Background
Doxorubicin (Dox) induces dose-dependent Dox–induced cardiotoxicity (DIC), but the chamber-specific molecular mechanisms remain unclear, as traditional analyses rely on whole-heart homogenates.
Methods
We established rat acute single–dose and chronic cumulative–dose DIC models, and separated left atrium (L–atrium) and left ventricle (L–ventricle) tissues for subsequent detection. Liquid chromatography–tandem mass spectrometry (LC–MS/MS) was used to quantify regional Dox tissue and serum concentrations. Histological HE and Masson’s staining were used to evaluate myocardial structural injury and collagen deposition. Integrated chamber-specific bulk proteomics, phosphoproteomics, and untargeted metabolomics were applied to systematically compare molecular perturbations between the L-atrium and L-ventricle. Two–way factorial statistical decomposition coupled with functional enrichment analysis was subsequently performed to identify both shared and chamber-specific molecular signatures.
