The Role of MicroRNAs in the Pathogenesis of Doxorubicin-Induced Vascular Remodeling

Area of Science:

• Cardiovascular Biology
• Molecular Oncology
• Pharmacology

Background:

• Doxorubicin (DOX) is a vital chemotherapy drug with known cardiovascular toxicity.
• This toxicity involves oxidative stress, mitochondrial dysfunction, inflammation, and altered autophagy, leading to heart failure and vascular remodeling.
• MicroRNAs (miRNAs) are increasingly recognized as key players in DOX-induced cardiotoxicity and vascular changes.

Purpose of the Study:

• To review the current understanding of miRNA dysregulation in response to Doxorubicin (DOX).
• To explore the dual role of miRNAs in cardiovascular pathology and tumor progression.
• To identify potential therapeutic strategies targeting miRNAs to mitigate DOX cardiotoxicity.

Main Methods:

• Literature review synthesizing existing research on miRNAs and DOX-induced cardiovascular effects.
• Analysis of miRNA involvement in signaling pathways regulating vascular homeostasis, angiogenesis, and endothelial-to-mesenchymal transition.
• Identification of specific miRNAs implicated in DOX cardiotoxicity and vascular remodeling.

Main Results:

• Doxorubicin (DOX) exposure leads to dysregulation of numerous miRNAs (e.g., miR-21, miR-22, miR-126).
• These miRNAs modulate critical signaling pathways (e.g., TGF-β/Smad, NF-κB, PI3K/AKT/Nrf2) affecting vascular remodeling and endothelial function.
• miRNAs exhibit a dual role, influencing both cardiovascular damage and potentially tumor growth.

Conclusions:

• MicroRNAs are crucial mediators of Doxorubicin (DOX)-induced cardiotoxicity and vascular remodeling.
• Targeting specific miRNAs or their pathways offers a promising therapeutic avenue to reduce DOX-related cardiovascular adverse effects.
• Further research is needed to fully elucidate the complex roles of miRNAs in this context for improved cancer therapy outcomes.