Atorvastatin Inhibits Endothelial PAI-1-Mediated Monocyte Migration and Alleviates Radiation-Induced Enteropathy

Area of Science:

• Radiation oncology
• Gastroenterology
• Vascular biology

Background:

• Radiotherapy for cancer and accidental radiation exposure can cause intestinal injury.
• Radiation disrupts gastrointestinal vascular homeostasis, leading to endothelial damage and senescence.
• Current treatments for radiation-induced enteropathy are limited.

Purpose of the Study:

• To investigate the potential of atorvastatin in mitigating radiation-induced enteropathy.
• To explore atorvastatin's effects on inflammatory responses and endothelial damage post-radiation.
• To elucidate the molecular mechanisms underlying atorvastatin's protective effects.

Main Methods:

• Utilized human umbilical vein endothelial cells (HUVECs) and a mouse model of radiation-induced enteropathy.
• Assessed the impact of atorvastatin on endothelial damage, PAI-1 regulation, and inflammatory markers.
• Investigated the role of the JNK/c-Jun signaling pathway in atorvastatin's mechanism of action.

Main Results:

• Atorvastatin mitigated radiation-induced endothelial damage and enteropathy in both in vitro and in vivo models.
• Atorvastatin significantly reduced plasminogen activator inhibitor-1 (PAI-1) production and secretion in irradiated HUVECs and mice.
• The drug's inhibitory effect on PAI-1 was mediated through the JNK/c-Jun signaling pathway.

Conclusions:

• Atorvastatin demonstrates radio-mitigating properties by protecting against radiation-induced intestinal injury.
• Targeting PAI-1 via atorvastatin offers a potential therapeutic strategy for radiation-induced enteropathy.
• Further investigation of atorvastatin as a radio-protector for patients receiving radiotherapy is warranted.