Kallistatin limits abdominal aortic aneurysm by attenuating generation of reactive oxygen species and apoptosis

Abstract Inflammation, vascular smooth muscle cell apoptosis and oxidative stress are believed to play important roles in abdominal aortic aneurysm (AAA) pathogenesis. Human kallistatin (KAL; gene SERPINA4) is a serine proteinase inhibitor previously shown to inhibit inflammation, apoptosis and oxid...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Smriti Murali Krishna, Jiaze Li, Yutang Wang, Corey S. Moran, Alexandra Trollope, Pacific Huynh, Roby Jose, Erik Biros, Jianxing Ma, Jonathan Golledge
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/397c6e28517446e49fbf89fa1ca7b4c8
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:397c6e28517446e49fbf89fa1ca7b4c8
record_format	dspace
spelling	oai:doaj.org-article:397c6e28517446e49fbf89fa1ca7b4c82021-12-02T19:04:01ZKallistatin limits abdominal aortic aneurysm by attenuating generation of reactive oxygen species and apoptosis10.1038/s41598-021-97042-82045-2322https://doaj.org/article/397c6e28517446e49fbf89fa1ca7b4c82021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97042-8https://doaj.org/toc/2045-2322Abstract Inflammation, vascular smooth muscle cell apoptosis and oxidative stress are believed to play important roles in abdominal aortic aneurysm (AAA) pathogenesis. Human kallistatin (KAL; gene SERPINA4) is a serine proteinase inhibitor previously shown to inhibit inflammation, apoptosis and oxidative stress. The aim of this study was to investigate the role of KAL in AAA through studies in experimental mouse models and patients. Serum KAL concentration was negatively associated with the diagnosis and growth of human AAA. Transgenic overexpression of the human KAL gene (KS-Tg) or administration of recombinant human KAL (rhKAL) inhibited AAA in the calcium phosphate (CaPO4) and subcutaneous angiotensin II (AngII) infusion mouse models. Upregulation of KAL in both models resulted in reduction in the severity of aortic elastin degradation, reduced markers of oxidative stress and less vascular smooth muscle apoptosis within the aorta. Administration of rhKAL to vascular smooth muscle cells incubated in the presence of AngII or in human AAA thrombus-conditioned media reduced apoptosis and downregulated markers of oxidative stress. These effects of KAL were associated with upregulation of Sirtuin 1 activity within the aortas of both KS-Tg mice and rodents receiving rhKAL. These results suggest KAL-Sirtuin 1 signalling limits aortic wall remodelling and aneurysm development through reductions in oxidative stress and vascular smooth muscle cell apoptosis. Upregulating KAL may be a novel therapeutic strategy for AAA.Smriti Murali KrishnaJiaze LiYutang WangCorey S. MoranAlexandra TrollopePacific HuynhRoby JoseErik BirosJianxing MaJonathan GolledgeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Smriti Murali Krishna Jiaze Li Yutang Wang Corey S. Moran Alexandra Trollope Pacific Huynh Roby Jose Erik Biros Jianxing Ma Jonathan Golledge Kallistatin limits abdominal aortic aneurysm by attenuating generation of reactive oxygen species and apoptosis
description	Abstract Inflammation, vascular smooth muscle cell apoptosis and oxidative stress are believed to play important roles in abdominal aortic aneurysm (AAA) pathogenesis. Human kallistatin (KAL; gene SERPINA4) is a serine proteinase inhibitor previously shown to inhibit inflammation, apoptosis and oxidative stress. The aim of this study was to investigate the role of KAL in AAA through studies in experimental mouse models and patients. Serum KAL concentration was negatively associated with the diagnosis and growth of human AAA. Transgenic overexpression of the human KAL gene (KS-Tg) or administration of recombinant human KAL (rhKAL) inhibited AAA in the calcium phosphate (CaPO4) and subcutaneous angiotensin II (AngII) infusion mouse models. Upregulation of KAL in both models resulted in reduction in the severity of aortic elastin degradation, reduced markers of oxidative stress and less vascular smooth muscle apoptosis within the aorta. Administration of rhKAL to vascular smooth muscle cells incubated in the presence of AngII or in human AAA thrombus-conditioned media reduced apoptosis and downregulated markers of oxidative stress. These effects of KAL were associated with upregulation of Sirtuin 1 activity within the aortas of both KS-Tg mice and rodents receiving rhKAL. These results suggest KAL-Sirtuin 1 signalling limits aortic wall remodelling and aneurysm development through reductions in oxidative stress and vascular smooth muscle cell apoptosis. Upregulating KAL may be a novel therapeutic strategy for AAA.
format	article
author	Smriti Murali Krishna Jiaze Li Yutang Wang Corey S. Moran Alexandra Trollope Pacific Huynh Roby Jose Erik Biros Jianxing Ma Jonathan Golledge
author_facet	Smriti Murali Krishna Jiaze Li Yutang Wang Corey S. Moran Alexandra Trollope Pacific Huynh Roby Jose Erik Biros Jianxing Ma Jonathan Golledge
author_sort	Smriti Murali Krishna
title	Kallistatin limits abdominal aortic aneurysm by attenuating generation of reactive oxygen species and apoptosis
title_short	Kallistatin limits abdominal aortic aneurysm by attenuating generation of reactive oxygen species and apoptosis
title_full	Kallistatin limits abdominal aortic aneurysm by attenuating generation of reactive oxygen species and apoptosis
title_fullStr	Kallistatin limits abdominal aortic aneurysm by attenuating generation of reactive oxygen species and apoptosis
title_full_unstemmed	Kallistatin limits abdominal aortic aneurysm by attenuating generation of reactive oxygen species and apoptosis
title_sort	kallistatin limits abdominal aortic aneurysm by attenuating generation of reactive oxygen species and apoptosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/397c6e28517446e49fbf89fa1ca7b4c8
work_keys_str_mv	AT smritimuralikrishna kallistatinlimitsabdominalaorticaneurysmbyattenuatinggenerationofreactiveoxygenspeciesandapoptosis AT jiazeli kallistatinlimitsabdominalaorticaneurysmbyattenuatinggenerationofreactiveoxygenspeciesandapoptosis AT yutangwang kallistatinlimitsabdominalaorticaneurysmbyattenuatinggenerationofreactiveoxygenspeciesandapoptosis AT coreysmoran kallistatinlimitsabdominalaorticaneurysmbyattenuatinggenerationofreactiveoxygenspeciesandapoptosis AT alexandratrollope kallistatinlimitsabdominalaorticaneurysmbyattenuatinggenerationofreactiveoxygenspeciesandapoptosis AT pacifichuynh kallistatinlimitsabdominalaorticaneurysmbyattenuatinggenerationofreactiveoxygenspeciesandapoptosis AT robyjose kallistatinlimitsabdominalaorticaneurysmbyattenuatinggenerationofreactiveoxygenspeciesandapoptosis AT erikbiros kallistatinlimitsabdominalaorticaneurysmbyattenuatinggenerationofreactiveoxygenspeciesandapoptosis AT jianxingma kallistatinlimitsabdominalaorticaneurysmbyattenuatinggenerationofreactiveoxygenspeciesandapoptosis AT jonathangolledge kallistatinlimitsabdominalaorticaneurysmbyattenuatinggenerationofreactiveoxygenspeciesandapoptosis
_version_	1718377203049168896

Kallistatin limits abdominal aortic aneurysm by attenuating generation of reactive oxygen species and apoptosis

Ejemplares similares