MicroRNAs play a critical role in doxorubicin-induced vascular remodeling and cardiotoxicity by influencing signaling pathways such as TGF-β/Smad, AMPKa/SIRT, and NF-κB.
Doxorubicin (DOX), a cornerstone chemotherapeutic agent, effectively combats various malignancies but is marred by significant cardiovascular toxicity, including endothelial damage, chronic heart failure, and vascular remodeling. These adverse effects, mediated by oxidative stress, mitochondrial dysfunction, inflammatory pathways, and dysregulated autophagy, underscore the need for precise therapeutic strategies. Emerging research highlights the critical role of microRNAs (miRNAs) in DOX-induced vascular remodeling and cardiotoxicity. miRNAs, such as miR-21, miR-22, miR-25, miR-126, miR-140-5p, miR-330-5p, miR-146, miR-143, miR-375, miR-125b, miR-451, miR-34a-5p, and miR-9, influence signaling pathways like TGF-β/Smad, AMPKa/SIRT, NF-κB, mTOR, VEGF, and PI3K/AKT/Nrf2, impacting vascular homeostasis, angiogenesis, and endothelial-to-mesenchymal transition. Despite existing studies, gaps remain in understanding the full spectrum of miRNAs involved and their downstream effects on vascular remodeling. This review synthesizes the current knowledge on miRNA dysregulation during DOX exposure, focusing on their dual roles in cardiovascular pathology and tumor progression. Strategies to reduce DOX cardiotoxicity include modulating miRNA expression to restore signaling balance, targeting pro-inflammatory and pro-fibrotic pathways, and leveraging miRNA inhibitors or mimics. This review aims to organize and integrate the existing knowledge on the role of miRNAs in vascular remodeling, particularly in the contexts of DOX treatment and the progression of various cardiovascular diseases, including their potential involvement in tumor growth.
Podyacheva et al. (Thu,) conducted a review in Doxorubicin-induced vascular remodeling and cardiotoxicity. MicroRNAs was evaluated. MicroRNAs play a critical role in doxorubicin-induced vascular remodeling and cardiotoxicity by influencing signaling pathways such as TGF-β/Smad, AMPKa/SIRT, and NF-κB.