MiRNA-Mediated Fibrosis in the Out-of-Target Heart following Partial-Body Irradiation

Area of Science:

• Cardiovascular Biology
• Radiation Oncology
• Molecular Biology

Background:

• Radiation exposure is linked to non-cancer diseases like radiation-induced heart disease (RIHD).
• Few studies investigate non-cancer disease risks from inhomogeneous radiation exposure and out-of-target effects.
• MicroRNAs (miRNAs) are implicated in disease pathogenesis, but their role in RIHD is underexplored.

Purpose of the Study:

• To investigate the role of miRNAs in the pathogenesis of radiation-induced heart disease (RIHD).
• To explore miRNA involvement in both directly and indirectly affected cardiac tissues following radiation exposure.

Main Methods:

• Whole-body irradiation (WBI) and partial-body irradiation (PBI) models in C57Bl/6J mice.
• MiRNome analysis at 15 days post-irradiation.
• Raman spectral analysis at 15 days and 6 months post-irradiation.
• In vitro co-culture system of irradiated skeletal muscle and cardiac cells.

Main Results:

• MyomiR family miRNAs were differentially expressed in WBI and PBI mouse hearts 15 days post-irradiation.
• Biochemical differences were observed in hearts from SI, WBI, and PBI groups at both time points.
• Cardiac fibrosis and myofibroblast activation were evident 6 months post-irradiation in WBI and PBI groups.
• miR-1/133a were identified as potential mediators of the abscopal effect in vitro.

Conclusions:

• MiRNAs, particularly myomiRs, play a significant role in the pathogenesis of RIHD.
• Radiation-induced cardiac fibrosis occurs months after exposure.
• miR-1/133a may mediate abscopal responses, suggesting potential miRNA-based therapeutic strategies for non-directly irradiated tissues.