Differences in Expression of Mitochondrial Complexes Due to Genetic Variants May Alter Sensitivity to Radiation-Induced Cardiac Dysfunction
Radiation therapy is received by over half of all cancer patients. However, radiation doses may be constricted due to normal tissue side effects. In thoracic cancers, including breast and lung cancers, cardiac radiation is a major concern in treatment planning. There are currently no biomarkers of r...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-03-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcvm.2020.00023/full |
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| author | Rachel A. Schlaak Anne Frei Gopika SenthilKumar Gopika SenthilKumar Shirng-Wern Tsaih Clive Wells Jyotsna Mishra Michael J. Flister Amadou K. S. Camara Carmen Bergom Carmen Bergom Carmen Bergom Carmen Bergom |
| author_facet | Rachel A. Schlaak Anne Frei Gopika SenthilKumar Gopika SenthilKumar Shirng-Wern Tsaih Clive Wells Jyotsna Mishra Michael J. Flister Amadou K. S. Camara Carmen Bergom Carmen Bergom Carmen Bergom Carmen Bergom |
| author_sort | Rachel A. Schlaak |
| collection | DOAJ |
| description | Radiation therapy is received by over half of all cancer patients. However, radiation doses may be constricted due to normal tissue side effects. In thoracic cancers, including breast and lung cancers, cardiac radiation is a major concern in treatment planning. There are currently no biomarkers of radiation-induced cardiotoxicity. Complex genetic modifiers can contribute to the risk of radiation-induced cardiotoxicities, yet these modifiers are largely unknown and poorly understood. We have previously reported the SS (Dahl salt-sensitive/Mcwi) rat strain is a highly sensitized model of radiation-induced cardiotoxicity compared to the more resistant Brown Norway (BN) rat strain. When rat chromosome 3 from the resistant BN rat strain is substituted into the SS background (SS.BN3 consomic), it significantly attenuates radiation-induced cardiotoxicity, demonstrating inherited genetic variants on rat chromosome 3 modify radiation sensitivity. Genes involved with mitochondrial function were differentially expressed in the hearts of SS and SS.BN3 rats 1 week after radiation. Here we further assessed differences in mitochondria-related genes between the sensitive SS and resistant SS.BN3 rats. We found mitochondrial-related gene expression differed in untreated hearts, while no differences in mitochondrial morphology were seen 1 week after localized heart radiation. At 12 weeks after localized cardiac radiation, differences in mitochondrial complex protein expression in the left ventricles were seen between the SS and SS.BN3 rats. These studies suggest that differences in mitochondrial gene expression caused by inherited genetic variants may contribute to differences in sensitivity to cardiac radiation. |
| first_indexed | 2024-12-11T13:58:50Z |
| format | Article |
| id | doaj.art-65dadfe43c554a2ea1132b514e1b65c7 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-11T13:58:50Z |
| publishDate | 2020-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-65dadfe43c554a2ea1132b514e1b65c72022-12-22T01:03:57ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2020-03-01710.3389/fcvm.2020.00023520585Differences in Expression of Mitochondrial Complexes Due to Genetic Variants May Alter Sensitivity to Radiation-Induced Cardiac DysfunctionRachel A. Schlaak0Anne Frei1Gopika SenthilKumar2Gopika SenthilKumar3Shirng-Wern Tsaih4Clive Wells5Jyotsna Mishra6Michael J. Flister7Amadou K. S. Camara8Carmen Bergom9Carmen Bergom10Carmen Bergom11Carmen Bergom12Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, United StatesMedical Scientist Training Program, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Medicine, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI, United StatesElectron Microscope Facility, Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, United StatesCardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, United States0Cancer Center, Medical College of Wisconsin, Milwaukee, WI, United StatesRadiation therapy is received by over half of all cancer patients. However, radiation doses may be constricted due to normal tissue side effects. In thoracic cancers, including breast and lung cancers, cardiac radiation is a major concern in treatment planning. There are currently no biomarkers of radiation-induced cardiotoxicity. Complex genetic modifiers can contribute to the risk of radiation-induced cardiotoxicities, yet these modifiers are largely unknown and poorly understood. We have previously reported the SS (Dahl salt-sensitive/Mcwi) rat strain is a highly sensitized model of radiation-induced cardiotoxicity compared to the more resistant Brown Norway (BN) rat strain. When rat chromosome 3 from the resistant BN rat strain is substituted into the SS background (SS.BN3 consomic), it significantly attenuates radiation-induced cardiotoxicity, demonstrating inherited genetic variants on rat chromosome 3 modify radiation sensitivity. Genes involved with mitochondrial function were differentially expressed in the hearts of SS and SS.BN3 rats 1 week after radiation. Here we further assessed differences in mitochondria-related genes between the sensitive SS and resistant SS.BN3 rats. We found mitochondrial-related gene expression differed in untreated hearts, while no differences in mitochondrial morphology were seen 1 week after localized heart radiation. At 12 weeks after localized cardiac radiation, differences in mitochondrial complex protein expression in the left ventricles were seen between the SS and SS.BN3 rats. These studies suggest that differences in mitochondrial gene expression caused by inherited genetic variants may contribute to differences in sensitivity to cardiac radiation.https://www.frontiersin.org/article/10.3389/fcvm.2020.00023/fullradiationradiation-induced heart damagemitochondriaconsomic ratsoxidative phosphorylationechocardiogram |
| spellingShingle | Rachel A. Schlaak Anne Frei Gopika SenthilKumar Gopika SenthilKumar Shirng-Wern Tsaih Clive Wells Jyotsna Mishra Michael J. Flister Amadou K. S. Camara Carmen Bergom Carmen Bergom Carmen Bergom Carmen Bergom Differences in Expression of Mitochondrial Complexes Due to Genetic Variants May Alter Sensitivity to Radiation-Induced Cardiac Dysfunction Frontiers in Cardiovascular Medicine radiation radiation-induced heart damage mitochondria consomic rats oxidative phosphorylation echocardiogram |
| title | Differences in Expression of Mitochondrial Complexes Due to Genetic Variants May Alter Sensitivity to Radiation-Induced Cardiac Dysfunction |
| title_full | Differences in Expression of Mitochondrial Complexes Due to Genetic Variants May Alter Sensitivity to Radiation-Induced Cardiac Dysfunction |
| title_fullStr | Differences in Expression of Mitochondrial Complexes Due to Genetic Variants May Alter Sensitivity to Radiation-Induced Cardiac Dysfunction |
| title_full_unstemmed | Differences in Expression of Mitochondrial Complexes Due to Genetic Variants May Alter Sensitivity to Radiation-Induced Cardiac Dysfunction |
| title_short | Differences in Expression of Mitochondrial Complexes Due to Genetic Variants May Alter Sensitivity to Radiation-Induced Cardiac Dysfunction |
| title_sort | differences in expression of mitochondrial complexes due to genetic variants may alter sensitivity to radiation induced cardiac dysfunction |
| topic | radiation radiation-induced heart damage mitochondria consomic rats oxidative phosphorylation echocardiogram |
| url | https://www.frontiersin.org/article/10.3389/fcvm.2020.00023/full |
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