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September 22, 2023Open Access

Short-term statin treatment reduces, and long-term statin treatment abolishes chronic vascular injury by radiation therapy

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Key result

In mice, short-term administration of pravastatin partially reduced chronic vascular injury after irradiation, whereas long-term administration for one year completely reversed the irradiation-induced changes in vascular reactivity.

Why the study?

Statin use during radiation therapy has been associated with reduced cardiovascular risk, but whether irradiation causes chronic vascular injury and whether short-term statins are sufficient to prevent it compared with long-term statins remains unclear.

Does pravastatin prevent chronic vascular injury in mice exposed to head-and-neck irradiation?

Population

C57Bl/6 mice exposed to 12 Gy x-ray head-and-neck irradiation

Comparison

Pravastatin for one additional day vs for one year after irradiation

Design

Preclinical animal study

Follow-up

One year

Authors

KAKarima Ait‐AissaXGXutong GuoMKMadelyn Klemmensen

Discussion

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Member takes

Overview

May support trials in irradiated patients; leaves open clinical translation from this mouse model.

Structured PICO

Does pravastatin prevent chronic vascular injury in mice exposed to head-and-neck irradiation?

P
Population
C57BL/6J mice aged 12-16 weeks exposed to 12 Gy head-and-neck irradiation and followed for one year to assess vascular reactivity and gene expression.
I
Intervention
Pravastatin (approx 30 mg/kg/day orally in drinking water) starting 72 hours before irradiation and continuing for either 24 hours after irradiation (short-term) or 12 months after irradiation (long-term)
C
Comparator
Vehicle only (filtered tap water) with irradiation, and sham-treated mice (non-irradiated) with vehicle or pravastatin
O
Outcome
Vascular reactivity (endothelium-dependent vasorelaxation and vasoconstriction) and altered gene expression in carotid arteries one year after irradiationsurrogate

In a mouse model, short-term pravastatin administration reduces, and long-term administration abolishes, chronic vascular injury and endothelial dysfunction one year after head-and-neck irradiation.

Limitations

  • Preclinical animal model; optimal duration of treatment in humans is unknown
  • Further studies needed to establish BK channel protein levels in smooth muscle cells
  • Need to study other channels relevant for vasoconstriction (Kv, KATP, L-VDCC)
  • The optimal duration of treatment in humans has yet to be determined
  • Need to fully establish the molecular mechanisms that contribute to enhanced constriction after IR

Cite This Study

Ait‐Aissa et al. (2023) studied Radiation-induced vascular injury. Pravastatin vs. Vehicle was evaluated on Vascular reactivity (endothelium-dependent vasorelaxation and vasoconstriction) of carotid arteries one year after irradiation. In mice, short-term administration of pravastatin partially reduced chronic vascular injury after irradiation, whereas long-term administration for one year completely reversed the irradiation-induced changes in vascular reactivity.

synapsesocial.com/papers/6a9ada42f437fe5ecd589891https://doi.org/10.1101/2023.09.20.558723
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Short‐Term Statin Treatment Reduces, and Long‐Term Statin Treatment Abolishes, Chronic Vascular Injury by Radiation Therapy2024 · 7 citations
  2. 2Mechanisms by which statins protect endothelial cells from radiation-induced injury in the carotid artery2023 · 15 citations
  3. 3Pravastatin Limits Endothelial Activation after Irradiation and Decreases the Resulting Inflammatory and Thrombotic Responses2005 · 120 citations
  4. 4A multimodality assessment of the protective capacity of statin therapy in a mouse model of radiation cardiotoxicity2023 · 8 citations
  5. 5Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation2015 · 33 citations