Journal article
Mechanisms by which statins protect endothelial cells from radiation-induced injury in the carotid artery
Frontiers in cardiovascular medicine, Vol.10, 1133315
06/01/2023
DOI: 10.3389/fcvm.2023.1133315
PMCID: PMC10315477
PMID: 37404737
Abstract
Background The incidental use of statins during radiation therapy has been associated with a reduced long-term risk of developing atherosclerotic cardiovascular disease. However, the mechanisms by which statins protect the vasculature from irradiation injury remain poorly understood. Objectives Identify the mechanisms by which the hydrophilic and lipophilic statins pravastatin and atorvastatin preserve endothelial function after irradiation. Methods Cultured human coronary and umbilical vein endothelial cells irradiated with 4 Gy and mice subjected to 12 Gy head-and-neck irradiation were pretreated with statins and tested for endothelial dysfunction, nitric oxide production, oxidative stress, and various mitochondrial phenotypes at 24 and 240 h after irradiation. Results Both pravastatin (hydrophilic) and atorvastatin (lipophilic) were sufficient to prevent the loss of endothelium-dependent relaxation of arteries after head-and-neck irradiation, preserve the production of nitric oxide by endothelial cells, and suppress the cytosolic reactive oxidative stress associated with irradiation. However, only pravastatin inhibited irradiation-induced production of mitochondrial superoxide; damage to the mitochondrial DNA; loss of electron transport chain activity; and expression of inflammatory markers. Conclusions Our findings reveal some mechanistic underpinnings of the vasoprotective effects of statins after irradiation. Whereas both pravastatin and atorvastatin can shield from endothelial dysfunction after irradiation, pravastatin additionally suppresses mitochondrial injury and inflammatory responses involving mitochondria. Clinical follow-up studies will be necessary to determine whether hydrophilic statins are more effective than their lipophilic counterparts in reducing the risk of cardiovascular disease in patients undergoing radiation therapy.
Details
- Title: Subtitle
- Mechanisms by which statins protect endothelial cells from radiation-induced injury in the carotid artery
- Creators
- Karima Ait-Aissa - University of IowaLinette N. Leng - University of IowaNathanial R. Lindsey - University of IowaXutong Guo - Abboud Cardiovascular Research Center, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, United StatesDenise Juhr - Abboud Cardiovascular Research Center, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, United StatesOlha M. Koval - University of IowaIsabella M. Grumbach - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Frontiers in cardiovascular medicine, Vol.10, 1133315
- DOI
- 10.3389/fcvm.2023.1133315
- PMID
- 37404737
- PMCID
- PMC10315477
- NLM abbreviation
- Front Cardiovasc Med
- eISSN
- 2297-055X
- Publisher
- Frontiers Media S.A
- Grant note
- award: R01 EY031544; award: 18IPA 34170003, 2021CDA 853499; award: I01 BX000163
- Language
- English
- Date published
- 06/01/2023
- Academic Unit
- Cardiovascular Medicine; Radiation Oncology; Anesthesia; Internal Medicine
- Record Identifier
- 9984436458302771
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