Abstract
Abstract 14966: Mechanisms of Protection From Radiation-Induced Endothelial Injury by Statins
Circulation (New York, N.Y.), Vol.146(S_1), p.A14966
11/08/2022
DOI: 10.1161/circ.146.suppl_1.14966
Abstract
Byline: Karima Ait-Aissa, INTERNAL MEDICINE, UNIVERSITY OF IOWA, Iowa City, IA; Olha Koval, INTERNAL MEDICINE, UNIVERSITE OF IOWA, Iowa City, IA; Nathanial Lindsey, INTERNAL MEDICINE, UNIVERSITE OF IOWA, Iowa City, IA; Linette Leng, INTERNAL MEDICINE, UNIVERSITY OF IOWA, Iowa City, IA; Isabella M Grumbach, INTERNAL MEDICINE, UNIVERSITE OF IOWA, Iowa City, IA Introduction: The incidental use of statins during radiation therapy has been associated with a decreased risk of long-term atherosclerotic cardiovascular (CV) disease. However, the mechanisms by which statins protect the vasculature from irradiation injury remain poorly understood. Hypothesis: Establish the mechanisms by which lipophilic and hydrophilic statins preserve endothelial function after irradiation. Methods: Cultured human coronary and umbilical vein endothelial cells irradiated with 4 Gy and mice on day 1 and 10 after head and neck irradiation with 12 Gy were assessed for endothelial dysfunction, nitric oxide and reactive oxidative stress production and various mitochondrial phenotypes. Results: Pretreatment of mice with pravastatin or atorvastatin prevented the loss of endothelium-dependent relaxation on day 1 and 10 after head and neck irradiation. Both statins inhibit the loss of nitric oxide, and the increase in cytosolic reactive oxidative stress in endothelial cells. However, only pravastatin blocked mitochondrial superoxide production, mitochondrial DNA damage and loss of electron complex activity. In contrast to atorvastatin, pravastatin also significantly reduced the expression of inflammatory markers TNF-ð, NFð¦B p65 and p50 after irradiation. Conclusions: Our findings provide mechanistic underpinnings for the vasoprotective effects of statins after irradiation. While lipo- and hydrophilic statins shield from endothelial dysfunction after irradiation, pravastatin also prevents mitochondrial injury and decreases an inflammatory response by actions in mitochondria. A correlation with clinical studies is necessary to determine whether hydrophilic statins, such as pravastatin reduce the risk of CV disease after irradiation in humans to a greater extent than lipophilic statins.
Details
- Title: Subtitle
- Abstract 14966: Mechanisms of Protection From Radiation-Induced Endothelial Injury by Statins
- Creators
- Karima Ait-AissaOlha KovalNathanial LindseyLinette LengIsabella M Grumbach
- Resource Type
- Abstract
- Publication Details
- Circulation (New York, N.Y.), Vol.146(S_1), p.A14966
- Publisher
- Lippincott Williams & Wilkins, WK Health
- DOI
- 10.1161/circ.146.suppl_1.14966
- ISSN
- 0009-7322
- eISSN
- 1524-4539
- Language
- English
- Date published
- 11/08/2022
- Description audience
- Professional
- Academic Unit
- Radiation Oncology; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984361721202771
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