Angiotensin II Induces Aortic Rupture and Dissection in Osteoprotegerin‐Deficient Mice
Background The biological mechanism of action for osteoprotegerin, a soluble decoy receptor for the receptor activator of nuclear factor‐kappa B ligand in the vascular structure, has not been elucidated. The study aim was to determine if osteoprotegerin affects aortic structural integrity in angiote...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-04-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.122.025336 |
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| author | Toshihiro Tsuruda Atsushi Yamashita Misa Otsu Masanori Koide Yuko Nakamichi Yoko Sekita‐Hatakeyama Kinta Hatakeyama Taro Funamoto Etsuo Chosa Yujiro Asada Nobuyuki Udagawa Johji Kato Kazuo Kitamura |
| author_facet | Toshihiro Tsuruda Atsushi Yamashita Misa Otsu Masanori Koide Yuko Nakamichi Yoko Sekita‐Hatakeyama Kinta Hatakeyama Taro Funamoto Etsuo Chosa Yujiro Asada Nobuyuki Udagawa Johji Kato Kazuo Kitamura |
| author_sort | Toshihiro Tsuruda |
| collection | DOAJ |
| description | Background The biological mechanism of action for osteoprotegerin, a soluble decoy receptor for the receptor activator of nuclear factor‐kappa B ligand in the vascular structure, has not been elucidated. The study aim was to determine if osteoprotegerin affects aortic structural integrity in angiotensin II (Ang II)‐induced hypertension. Methods and Results Mortality was higher (P<0.0001 by log‐rank test) in 8‐week‐old male homozygotes of osteoprotegerin gene‐knockout mice given subcutaneous administration of Ang II for 28 days, with an incidence of 21% fatal aortic rupture and 23% aortic dissection, than in age‐matched wild‐type mice. Ang II‐infused aorta of wild‐type mice showed that osteoprotegerin immunoreactivity was present with proteoglycan. The absence of osteoprotegerin was associated with decreased medial and adventitial thickness and increased numbers of elastin breaks as well as with increased periostin expression and soluble receptor activator of nuclear factor‐kappa B ligand concentrations. PEGylated human recombinant osteoprotegerin administration decreased all‐cause mortality (P<0.001 by log‐rank test), the incidence of fatal aortic rupture (P=0.08), and aortic dissection (P<0.001) with decreasing numbers of elastin breaks, periostin expressions, and soluble receptor activator of nuclear factor‐kappa B ligand concentrations in Ang II‐infused osteoprotegerin gene‐knockout mice. Conclusions These data suggest that osteoprotegerin protects against aortic rupture and dissection in Ang II‐induced hypertension by inhibiting receptor activator of nuclear factor‐kappa B ligand activity and periostin expression. |
| first_indexed | 2024-03-07T23:25:26Z |
| format | Article |
| id | doaj.art-225fb59da20e4b74987309e83af4e1a3 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-03-07T23:25:26Z |
| publishDate | 2022-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-225fb59da20e4b74987309e83af4e1a32024-02-21T04:32:43ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802022-04-0111810.1161/JAHA.122.025336Angiotensin II Induces Aortic Rupture and Dissection in Osteoprotegerin‐Deficient MiceToshihiro Tsuruda0Atsushi Yamashita1Misa Otsu2Masanori Koide3Yuko Nakamichi4Yoko Sekita‐Hatakeyama5Kinta Hatakeyama6Taro Funamoto7Etsuo Chosa8Yujiro Asada9Nobuyuki Udagawa10Johji Kato11Kazuo Kitamura12Division of Internal Medicine, Cardiovascular Medicine and Nephrology Faculty of Medicine University of Miyazaki JapanDepartment of Pathology Faculty of Medicine University of Miyazaki JapanDivision of Internal Medicine, Cardiovascular Medicine and Nephrology Faculty of Medicine University of Miyazaki JapanInstitute for Oral Science Matsumoto Dental University Nagano JapanInstitute for Oral Science Matsumoto Dental University Nagano JapanDepartment of Diagnostic Pathology Nara Medical University Nara JapanDepartment of Pathology National Cerebral and Cardiovascular Center Osaka JapanDivision of Orthopedic Surgery Department of Medicine of Sensory and Motor Organs Faculty of Medicine University of Miyazaki JapanDivision of Orthopedic Surgery Department of Medicine of Sensory and Motor Organs Faculty of Medicine University of Miyazaki JapanDepartment of Pathology Faculty of Medicine University of Miyazaki JapanDepartment of Biochemistry Matsumoto Dental University Nagano JapanFrontier Science Research Center University of Miyazaki JapanFrontier Science Research Center University of Miyazaki JapanBackground The biological mechanism of action for osteoprotegerin, a soluble decoy receptor for the receptor activator of nuclear factor‐kappa B ligand in the vascular structure, has not been elucidated. The study aim was to determine if osteoprotegerin affects aortic structural integrity in angiotensin II (Ang II)‐induced hypertension. Methods and Results Mortality was higher (P<0.0001 by log‐rank test) in 8‐week‐old male homozygotes of osteoprotegerin gene‐knockout mice given subcutaneous administration of Ang II for 28 days, with an incidence of 21% fatal aortic rupture and 23% aortic dissection, than in age‐matched wild‐type mice. Ang II‐infused aorta of wild‐type mice showed that osteoprotegerin immunoreactivity was present with proteoglycan. The absence of osteoprotegerin was associated with decreased medial and adventitial thickness and increased numbers of elastin breaks as well as with increased periostin expression and soluble receptor activator of nuclear factor‐kappa B ligand concentrations. PEGylated human recombinant osteoprotegerin administration decreased all‐cause mortality (P<0.001 by log‐rank test), the incidence of fatal aortic rupture (P=0.08), and aortic dissection (P<0.001) with decreasing numbers of elastin breaks, periostin expressions, and soluble receptor activator of nuclear factor‐kappa B ligand concentrations in Ang II‐infused osteoprotegerin gene‐knockout mice. Conclusions These data suggest that osteoprotegerin protects against aortic rupture and dissection in Ang II‐induced hypertension by inhibiting receptor activator of nuclear factor‐kappa B ligand activity and periostin expression.https://www.ahajournals.org/doi/10.1161/JAHA.122.025336aortic dissectionelastinextracellular matrixproteoglycan |
| spellingShingle | Toshihiro Tsuruda Atsushi Yamashita Misa Otsu Masanori Koide Yuko Nakamichi Yoko Sekita‐Hatakeyama Kinta Hatakeyama Taro Funamoto Etsuo Chosa Yujiro Asada Nobuyuki Udagawa Johji Kato Kazuo Kitamura Angiotensin II Induces Aortic Rupture and Dissection in Osteoprotegerin‐Deficient Mice Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease aortic dissection elastin extracellular matrix proteoglycan |
| title | Angiotensin II Induces Aortic Rupture and Dissection in Osteoprotegerin‐Deficient Mice |
| title_full | Angiotensin II Induces Aortic Rupture and Dissection in Osteoprotegerin‐Deficient Mice |
| title_fullStr | Angiotensin II Induces Aortic Rupture and Dissection in Osteoprotegerin‐Deficient Mice |
| title_full_unstemmed | Angiotensin II Induces Aortic Rupture and Dissection in Osteoprotegerin‐Deficient Mice |
| title_short | Angiotensin II Induces Aortic Rupture and Dissection in Osteoprotegerin‐Deficient Mice |
| title_sort | angiotensin ii induces aortic rupture and dissection in osteoprotegerin deficient mice |
| topic | aortic dissection elastin extracellular matrix proteoglycan |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.122.025336 |
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