Fludrocortisone Induces Aortic Pathologies in Mice
Background and Objective: In an experiment designed to explore the mechanisms of fludrocortisone-induced high blood pressure, we serendipitously observed aortic aneurysms in mice infused with fludrocortisone. The purpose of this study was to investigate whether fludrocortisone induces aortic patholo...
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| Format: | Article |
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MDPI AG
2022-06-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/6/825 |
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| author | Dien Ye Congqing Wu Hui Chen Ching-Ling Liang Deborah A. Howatt Michael K. Franklin Jessica J. Moorleghen Samuel C. Tyagi Estrellita Uijl A. H. Jan Danser Hisashi Sawada Alan Daugherty Hong S. Lu |
| author_facet | Dien Ye Congqing Wu Hui Chen Ching-Ling Liang Deborah A. Howatt Michael K. Franklin Jessica J. Moorleghen Samuel C. Tyagi Estrellita Uijl A. H. Jan Danser Hisashi Sawada Alan Daugherty Hong S. Lu |
| author_sort | Dien Ye |
| collection | DOAJ |
| description | Background and Objective: In an experiment designed to explore the mechanisms of fludrocortisone-induced high blood pressure, we serendipitously observed aortic aneurysms in mice infused with fludrocortisone. The purpose of this study was to investigate whether fludrocortisone induces aortic pathologies in both normocholesterolemic and hypercholesterolemic mice. Methods and Results: Male adult C57BL/6J mice were infused with either vehicle (85% polyethylene glycol 400 (PEG-400) and 15% dimethyl sulfoxide (DMSO); <i>n</i> = 5) or fludrocortisone (12 mg/kg/day dissolved in 85% PEG-400 and 15% DMSO; <i>n</i> = 15) for 28 days. Fludrocortisone-infused mice had higher systolic blood pressure, compared to mice infused with vehicle. Fludrocortisone induced aortic pathologies in 4 of 15 mice with 3 having pathologies in the ascending and aortic arch regions and 1 having pathology in both the ascending and descending thoracic aorta. No pathologies were noted in abdominal aortas. Subsequently, we infused either vehicle (<i>n</i> = 5/group) or fludrocortisone (<i>n</i> = 15/group) into male ApoE <sup>−/−</sup> mice fed a normal laboratory diet or LDL receptor <sup>−/−</sup> mice fed either normal or Western diet. Fludrocortisone increased systolic blood pressure, irrespective of mouse strain or diet. In ApoE <sup>−/−</sup> mice infused with fludrocortisone, 2 of 15 mice had ascending aortic pathologies, but no mice had abdominal aortic pathologies. In LDL receptor <sup>−/−</sup> mice fed normal diet, 5 had ascending/arch pathologies and 1 had pathologies in the ascending, arch, and suprarenal aortic regions. In LDL receptor <sup>−/−</sup> mice fed Western diet, 2 died of aortic rupture in either the descending thoracic or abdominal region, and 2 of the 13 survived mice had ascending/arch aortic pathologies. Aortic pathologies included hemorrhage, wall thickening or thinning, or dilation. Only ascending aortic diameter in LDLR <sup>−/−</sup> mice fed Western diet reached statistical significance, compared to their vehicle. Conclusion: Fludrocortisone induces aortic pathologies independent of hypercholesterolemia. As indicated by the findings in mouse studies, people who are taking or have taken fludrocortisone might have an increased risk of aortic pathologies. |
| first_indexed | 2024-03-10T00:17:44Z |
| format | Article |
| id | doaj.art-38c5d62cb2f04a0b91bea96eb2f18cb4 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T00:17:44Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-38c5d62cb2f04a0b91bea96eb2f18cb42023-11-23T15:47:38ZengMDPI AGBiomolecules2218-273X2022-06-0112682510.3390/biom12060825Fludrocortisone Induces Aortic Pathologies in MiceDien Ye0Congqing Wu1Hui Chen2Ching-Ling Liang3Deborah A. Howatt4Michael K. Franklin5Jessica J. Moorleghen6Samuel C. Tyagi7Estrellita Uijl8A. H. Jan Danser9Hisashi Sawada10Alan Daugherty11Hong S. Lu12Saha Cardiovascular Research Center, Lexington, KY 40536, USASaha Cardiovascular Research Center, Lexington, KY 40536, USASaha Cardiovascular Research Center, Lexington, KY 40536, USASaha Cardiovascular Research Center, Lexington, KY 40536, USASaha Cardiovascular Research Center, Lexington, KY 40536, USASaha Cardiovascular Research Center, Lexington, KY 40536, USASaha Cardiovascular Research Center, Lexington, KY 40536, USASaha Cardiovascular Research Center, Lexington, KY 40536, USADivision of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus University Medical Center, 3015 CN Rotterdam, The NetherlandsDivision of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus University Medical Center, 3015 CN Rotterdam, The NetherlandsSaha Cardiovascular Research Center, Lexington, KY 40536, USASaha Cardiovascular Research Center, Lexington, KY 40536, USASaha Cardiovascular Research Center, Lexington, KY 40536, USABackground and Objective: In an experiment designed to explore the mechanisms of fludrocortisone-induced high blood pressure, we serendipitously observed aortic aneurysms in mice infused with fludrocortisone. The purpose of this study was to investigate whether fludrocortisone induces aortic pathologies in both normocholesterolemic and hypercholesterolemic mice. Methods and Results: Male adult C57BL/6J mice were infused with either vehicle (85% polyethylene glycol 400 (PEG-400) and 15% dimethyl sulfoxide (DMSO); <i>n</i> = 5) or fludrocortisone (12 mg/kg/day dissolved in 85% PEG-400 and 15% DMSO; <i>n</i> = 15) for 28 days. Fludrocortisone-infused mice had higher systolic blood pressure, compared to mice infused with vehicle. Fludrocortisone induced aortic pathologies in 4 of 15 mice with 3 having pathologies in the ascending and aortic arch regions and 1 having pathology in both the ascending and descending thoracic aorta. No pathologies were noted in abdominal aortas. Subsequently, we infused either vehicle (<i>n</i> = 5/group) or fludrocortisone (<i>n</i> = 15/group) into male ApoE <sup>−/−</sup> mice fed a normal laboratory diet or LDL receptor <sup>−/−</sup> mice fed either normal or Western diet. Fludrocortisone increased systolic blood pressure, irrespective of mouse strain or diet. In ApoE <sup>−/−</sup> mice infused with fludrocortisone, 2 of 15 mice had ascending aortic pathologies, but no mice had abdominal aortic pathologies. In LDL receptor <sup>−/−</sup> mice fed normal diet, 5 had ascending/arch pathologies and 1 had pathologies in the ascending, arch, and suprarenal aortic regions. In LDL receptor <sup>−/−</sup> mice fed Western diet, 2 died of aortic rupture in either the descending thoracic or abdominal region, and 2 of the 13 survived mice had ascending/arch aortic pathologies. Aortic pathologies included hemorrhage, wall thickening or thinning, or dilation. Only ascending aortic diameter in LDLR <sup>−/−</sup> mice fed Western diet reached statistical significance, compared to their vehicle. Conclusion: Fludrocortisone induces aortic pathologies independent of hypercholesterolemia. As indicated by the findings in mouse studies, people who are taking or have taken fludrocortisone might have an increased risk of aortic pathologies.https://www.mdpi.com/2218-273X/12/6/825aortic aneurysmsaortic dissectionfludrocortisoneangiotensinhypercholesterolemiamouse |
| spellingShingle | Dien Ye Congqing Wu Hui Chen Ching-Ling Liang Deborah A. Howatt Michael K. Franklin Jessica J. Moorleghen Samuel C. Tyagi Estrellita Uijl A. H. Jan Danser Hisashi Sawada Alan Daugherty Hong S. Lu Fludrocortisone Induces Aortic Pathologies in Mice Biomolecules aortic aneurysms aortic dissection fludrocortisone angiotensin hypercholesterolemia mouse |
| title | Fludrocortisone Induces Aortic Pathologies in Mice |
| title_full | Fludrocortisone Induces Aortic Pathologies in Mice |
| title_fullStr | Fludrocortisone Induces Aortic Pathologies in Mice |
| title_full_unstemmed | Fludrocortisone Induces Aortic Pathologies in Mice |
| title_short | Fludrocortisone Induces Aortic Pathologies in Mice |
| title_sort | fludrocortisone induces aortic pathologies in mice |
| topic | aortic aneurysms aortic dissection fludrocortisone angiotensin hypercholesterolemia mouse |
| url | https://www.mdpi.com/2218-273X/12/6/825 |
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