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Inhibition of smooth muscle cell death by Angiotensin 1-7 protects against abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) represents a debilitating vascular disease characterized by aortic dilatation and wall rupture if it remains untreated. We aimed to determine the effects of Ang 1-7 in a murine model of AAA and to investigate the molecular mechanisms involved. Eight- to 10-week-old ap...

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Autores principales: Jadli, Anshul S., Gomes, Karina P., Ballasy, Noura N., Wijesuriya, Tishani Methsala, Belke, Darrell, Fedak, Paul W.M., Patel, Vaibhav B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10695742/
https://www.ncbi.nlm.nih.gov/pubmed/37947205
http://dx.doi.org/10.1042/BSR20230718
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author Jadli, Anshul S.
Gomes, Karina P.
Ballasy, Noura N.
Wijesuriya, Tishani Methsala
Belke, Darrell
Fedak, Paul W.M.
Patel, Vaibhav B.
author_facet Jadli, Anshul S.
Gomes, Karina P.
Ballasy, Noura N.
Wijesuriya, Tishani Methsala
Belke, Darrell
Fedak, Paul W.M.
Patel, Vaibhav B.
author_sort Jadli, Anshul S.
collection PubMed
description Abdominal aortic aneurysm (AAA) represents a debilitating vascular disease characterized by aortic dilatation and wall rupture if it remains untreated. We aimed to determine the effects of Ang 1-7 in a murine model of AAA and to investigate the molecular mechanisms involved. Eight- to 10-week-old apolipoprotein E-deficient mice (ApoEKO) were infused with Ang II (1.44 mg/kg/day, s.c.) and treated with Ang 1-7 (0.576 mg/kg/day, i.p.). Echocardiographic and histological analyses showed abdominal aortic dilatation and extracellular matrix remodeling in Ang II-infused mice. Treatment with Ang 1-7 led to suppression of Ang II-induced aortic dilatation in the abdominal aorta. The immunofluorescence imaging exhibited reduced smooth muscle cell (SMC) density in the abdominal aorta. The abdominal aortic SMCs from ApoEKO mice exhibited markedly increased apoptosis in response to Ang II. Ang 1-7 attenuated cell death, as evident by increased SMC density in the aorta and reduced annexin V/propidium iodide-positive cells in flow cytometric analysis. Gene expression analysis for contractile and synthetic phenotypes of abdominal SMCs showed preservation of contractile phenotype by Ang 1-7 treatment. Molecular analyses identified increased mitochondrial fission, elevated cellular and mitochondrial reactive oxygen species (ROS) levels, and apoptosis-associated proteins, including cytochrome c, in Ang II-treated aortic SMCs. Ang 1-7 mitigated Ang II-induced mitochondrial fission, ROS generation, and levels of pro-apoptotic proteins, resulting in decreased cell death of aortic SMCs. These results highlight a critical vasculo-protective role of Ang 1-7 in a degenerative aortic disease; increased Ang 1-7 activity may provide a promising therapeutic strategy against the progression of AAA.
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spelling pubmed-106957422023-12-06 Inhibition of smooth muscle cell death by Angiotensin 1-7 protects against abdominal aortic aneurysm Jadli, Anshul S. Gomes, Karina P. Ballasy, Noura N. Wijesuriya, Tishani Methsala Belke, Darrell Fedak, Paul W.M. Patel, Vaibhav B. Biosci Rep Cardiovascular System & Vascular Biology Abdominal aortic aneurysm (AAA) represents a debilitating vascular disease characterized by aortic dilatation and wall rupture if it remains untreated. We aimed to determine the effects of Ang 1-7 in a murine model of AAA and to investigate the molecular mechanisms involved. Eight- to 10-week-old apolipoprotein E-deficient mice (ApoEKO) were infused with Ang II (1.44 mg/kg/day, s.c.) and treated with Ang 1-7 (0.576 mg/kg/day, i.p.). Echocardiographic and histological analyses showed abdominal aortic dilatation and extracellular matrix remodeling in Ang II-infused mice. Treatment with Ang 1-7 led to suppression of Ang II-induced aortic dilatation in the abdominal aorta. The immunofluorescence imaging exhibited reduced smooth muscle cell (SMC) density in the abdominal aorta. The abdominal aortic SMCs from ApoEKO mice exhibited markedly increased apoptosis in response to Ang II. Ang 1-7 attenuated cell death, as evident by increased SMC density in the aorta and reduced annexin V/propidium iodide-positive cells in flow cytometric analysis. Gene expression analysis for contractile and synthetic phenotypes of abdominal SMCs showed preservation of contractile phenotype by Ang 1-7 treatment. Molecular analyses identified increased mitochondrial fission, elevated cellular and mitochondrial reactive oxygen species (ROS) levels, and apoptosis-associated proteins, including cytochrome c, in Ang II-treated aortic SMCs. Ang 1-7 mitigated Ang II-induced mitochondrial fission, ROS generation, and levels of pro-apoptotic proteins, resulting in decreased cell death of aortic SMCs. These results highlight a critical vasculo-protective role of Ang 1-7 in a degenerative aortic disease; increased Ang 1-7 activity may provide a promising therapeutic strategy against the progression of AAA. Portland Press Ltd. 2023-11-30 /pmc/articles/PMC10695742/ /pubmed/37947205 http://dx.doi.org/10.1042/BSR20230718 Text en © 2023 The Author(s). https://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Cardiovascular System & Vascular Biology
Jadli, Anshul S.
Gomes, Karina P.
Ballasy, Noura N.
Wijesuriya, Tishani Methsala
Belke, Darrell
Fedak, Paul W.M.
Patel, Vaibhav B.
Inhibition of smooth muscle cell death by Angiotensin 1-7 protects against abdominal aortic aneurysm
title Inhibition of smooth muscle cell death by Angiotensin 1-7 protects against abdominal aortic aneurysm
title_full Inhibition of smooth muscle cell death by Angiotensin 1-7 protects against abdominal aortic aneurysm
title_fullStr Inhibition of smooth muscle cell death by Angiotensin 1-7 protects against abdominal aortic aneurysm
title_full_unstemmed Inhibition of smooth muscle cell death by Angiotensin 1-7 protects against abdominal aortic aneurysm
title_short Inhibition of smooth muscle cell death by Angiotensin 1-7 protects against abdominal aortic aneurysm
title_sort inhibition of smooth muscle cell death by angiotensin 1-7 protects against abdominal aortic aneurysm
topic Cardiovascular System & Vascular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10695742/
https://www.ncbi.nlm.nih.gov/pubmed/37947205
http://dx.doi.org/10.1042/BSR20230718
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