Podyacheva Ekaterina, Snezhkova Julia, Onopchenko Anatoliya, Dyachuk Vyacheslav, Toropova Yana
Almazov National Medical Research Centre, Ministry of Health of the Russian Federation, 197341 Saint-Petersburg, Russia.
Int J Mol Sci. 2024 Dec 12;25(24):13335. doi: 10.3390/ijms252413335.
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.
阿霉素（DOX）是一种基石性化疗药物，能有效对抗多种恶性肿瘤，但存在严重的心血管毒性，包括内皮损伤、慢性心力衰竭和血管重塑。这些由氧化应激、线粒体功能障碍、炎症途径和自噬失调介导的不良反应，凸显了精确治疗策略的必要性。新兴研究强调了微小RNA（miRNA）在DOX诱导的血管重塑和心脏毒性中的关键作用。诸如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和miR-9等miRNA，会影响TGF-β/Smad、AMPKa/SIRT、NF-κB、mTOR、VEGF和PI3K/AKT/Nrf2等信号通路，影响血管稳态、血管生成和内皮-间充质转化。尽管已有研究，但在全面了解所涉及的miRNA及其对血管重塑的下游影响方面仍存在差距。本综述综合了当前关于DOX暴露期间miRNA失调的知识，重点关注它们在心血管病理和肿瘤进展中的双重作用。降低DOX心脏毒性的策略包括调节miRNA表达以恢复信号平衡、靶向促炎和促纤维化途径，以及利用miRNA抑制剂或模拟物。本综述旨在整理和整合关于miRNA在血管重塑中的作用的现有知识，特别是在DOX治疗和各种心血管疾病进展的背景下，包括它们在肿瘤生长中的潜在参与。
