Short-Term Statin Treatment Reduces, and Long-Term Statin Treatment Abolishes, Chronic Vascular Injury by Radiation Therapy.

Autor: Ait-Aissa K; Department of Biomedical Sciences, College of Dental Medicine Lincoln Memorial University Knoxville TN USA., Guo X; Abboud Cardiovascular Research Center, Department of Internal Medicine, Carver College of Medicine University of Iowa Iowa City IA USA., Klemmensen M; Abboud Cardiovascular Research Center, Department of Internal Medicine, Carver College of Medicine University of Iowa Iowa City IA USA., Juhr D; Abboud Cardiovascular Research Center, Department of Internal Medicine, Carver College of Medicine University of Iowa Iowa City IA USA., Leng LN; Abboud Cardiovascular Research Center, Department of Internal Medicine, Carver College of Medicine University of Iowa Iowa City IA USA., Koval OM; Abboud Cardiovascular Research Center, Department of Internal Medicine, Carver College of Medicine University of Iowa Iowa City IA USA., Grumbach IM; Abboud Cardiovascular Research Center, Department of Internal Medicine, Carver College of Medicine University of Iowa Iowa City IA USA.; Free Radical and Radiation Biology Program, Department of Radiation Oncology, Carver College of Medicine University of Iowa Iowa City IA USA.; Iowa City VA Healthcare System Iowa City IA USA.
Jazyk: angličtina
Zdroj: Journal of the American Heart Association [J Am Heart Assoc] 2024 Jul 02; Vol. 13 (13), pp. e033558. Date of Electronic Publication: 2024 Jun 21.
DOI: 10.1161/JAHA.123.033558
Abstrakt: Background: The incidental use of statins during radiation therapy has been associated with a reduced long-term risk of developing atherosclerotic cardiovascular disease. We examined whether irradiation causes chronic vascular injury and whether short-term administration of statins during and after irradiation is sufficient to prevent chronic injury compared with long-term administration.
Methods and Results: C57Bl/6 mice were pretreated with pravastatin for 72 hours and then exposed to 12 Gy X-ray head-and-neck irradiation. Pravastatin was then administered either for an additional 24 hours or for 1 year. Carotid arteries were tested for vascular reactivity, altered gene expression, and collagen deposition 1 year after irradiation. Treatment with pravastatin for 24 hours after irradiation reduced the loss of endothelium-dependent vasorelaxation and protected against enhanced vasoconstriction. Expression of markers associated with inflammation (NFκB p65 [phospho-nuclear factor kappa B p65] and TNF-α [tumor necrosis factor alpha]) and with oxidative stress (NADPH oxidases 2 and 4) were lowered and subunits of the voltage and Ca 2+ activated K + BK channel (potassium calcium-activated channel subfamily M alpha 1 and potassium calcium-activated channel subfamily M regulatory beta subunit 1) in the carotid artery were modulated. Treatment with pravastatin for 1 year after irradiation completely reversed irradiation-induced changes.
Conclusions: Short-term administration of pravastatin is sufficient to reduce chronic vascular injury at 1 year after irradiation. Long-term administration eliminates the effects of irradiation. These findings suggest that a prospective treatment strategy involving statins could be effective in patients undergoing radiation therapy. The optimal duration of treatment in humans has yet to be determined.
Databáze: MEDLINE
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