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Sirtuin 3 Deficiency Accelerates Hypertensive Cardiac Remodeling by Impairing Angiogenesis

BACKGROUND: Emerging evidence indicates that impaired angiogenesis may contribute to hypertension‐induced cardiac remodeling. The nicotinamide adenine dinucleotide–dependent deacetylase Sirtuin 3 (SIRT3) has the potential to modulate angiogenesis, but this has not been confirmed. As such, the aim of...

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Autores principales: Wei, Tong, Huang, Gaojian, Gao, Jing, Huang, Chenglin, Sun, Mengwei, Wu, Jian, Bu, Juan, Shen, Weili
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5586452/
https://www.ncbi.nlm.nih.gov/pubmed/28862956
http://dx.doi.org/10.1161/JAHA.117.006114
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author Wei, Tong
Huang, Gaojian
Gao, Jing
Huang, Chenglin
Sun, Mengwei
Wu, Jian
Bu, Juan
Shen, Weili
author_facet Wei, Tong
Huang, Gaojian
Gao, Jing
Huang, Chenglin
Sun, Mengwei
Wu, Jian
Bu, Juan
Shen, Weili
author_sort Wei, Tong
collection PubMed
description BACKGROUND: Emerging evidence indicates that impaired angiogenesis may contribute to hypertension‐induced cardiac remodeling. The nicotinamide adenine dinucleotide–dependent deacetylase Sirtuin 3 (SIRT3) has the potential to modulate angiogenesis, but this has not been confirmed. As such, the aim of this study was to examine the relationship between SIRT3‐mediated angiogenesis and cardiac remodeling. METHODS AND RESULTS: Our experiments were performed on SIRT3 knockout and age‐matched wild‐type mice infused with angiotensin II (1400 ng/kg per minute) or saline for 14 days. After angiotensin II infusion, SIRT3 knockout mice developed more severe microvascular rarefaction and functional hypoxia in cardiac tissues compared with wild‐type mice. These events were concomitant with mitochondrial dysfunction and enhanced collagen I and collagen III expression, leading to cardiac fibrosis. Silencing SIRT3 facilitated angiotensin II–induced aberrant Pink/Parkin acetylation and impaired mitophagy, while excessive mitochondrial reactive oxygen species generation limited angiogenic capacity in primary mouse cardiac microvascular endothelial cells. Moreover, SIRT3 overexpression in cardiac microvascular endothelial cells enhanced Pink/Parkin‐mediated mitophagy, attenuated mitochondrial reactive oxygen species generation, and restored vessel sprouting and tube formation. In parallel, endothelial cell–specific SIRT3 transgenic mice showed decreased fibrosis, as well as improved cardiac function and microvascular network, compared with wild‐type mice with similar stimuli. CONCLUSIONS: Collectively, these findings suggest that SIRT3 could promote angiogenesis through attenuating mitochondrial dysfunction caused by defective mitophagy.
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spelling pubmed-55864522017-09-11 Sirtuin 3 Deficiency Accelerates Hypertensive Cardiac Remodeling by Impairing Angiogenesis Wei, Tong Huang, Gaojian Gao, Jing Huang, Chenglin Sun, Mengwei Wu, Jian Bu, Juan Shen, Weili J Am Heart Assoc Original Research BACKGROUND: Emerging evidence indicates that impaired angiogenesis may contribute to hypertension‐induced cardiac remodeling. The nicotinamide adenine dinucleotide–dependent deacetylase Sirtuin 3 (SIRT3) has the potential to modulate angiogenesis, but this has not been confirmed. As such, the aim of this study was to examine the relationship between SIRT3‐mediated angiogenesis and cardiac remodeling. METHODS AND RESULTS: Our experiments were performed on SIRT3 knockout and age‐matched wild‐type mice infused with angiotensin II (1400 ng/kg per minute) or saline for 14 days. After angiotensin II infusion, SIRT3 knockout mice developed more severe microvascular rarefaction and functional hypoxia in cardiac tissues compared with wild‐type mice. These events were concomitant with mitochondrial dysfunction and enhanced collagen I and collagen III expression, leading to cardiac fibrosis. Silencing SIRT3 facilitated angiotensin II–induced aberrant Pink/Parkin acetylation and impaired mitophagy, while excessive mitochondrial reactive oxygen species generation limited angiogenic capacity in primary mouse cardiac microvascular endothelial cells. Moreover, SIRT3 overexpression in cardiac microvascular endothelial cells enhanced Pink/Parkin‐mediated mitophagy, attenuated mitochondrial reactive oxygen species generation, and restored vessel sprouting and tube formation. In parallel, endothelial cell–specific SIRT3 transgenic mice showed decreased fibrosis, as well as improved cardiac function and microvascular network, compared with wild‐type mice with similar stimuli. CONCLUSIONS: Collectively, these findings suggest that SIRT3 could promote angiogenesis through attenuating mitochondrial dysfunction caused by defective mitophagy. John Wiley and Sons Inc. 2017-08-19 /pmc/articles/PMC5586452/ /pubmed/28862956 http://dx.doi.org/10.1161/JAHA.117.006114 Text en © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Research
Wei, Tong
Huang, Gaojian
Gao, Jing
Huang, Chenglin
Sun, Mengwei
Wu, Jian
Bu, Juan
Shen, Weili
Sirtuin 3 Deficiency Accelerates Hypertensive Cardiac Remodeling by Impairing Angiogenesis
title Sirtuin 3 Deficiency Accelerates Hypertensive Cardiac Remodeling by Impairing Angiogenesis
title_full Sirtuin 3 Deficiency Accelerates Hypertensive Cardiac Remodeling by Impairing Angiogenesis
title_fullStr Sirtuin 3 Deficiency Accelerates Hypertensive Cardiac Remodeling by Impairing Angiogenesis
title_full_unstemmed Sirtuin 3 Deficiency Accelerates Hypertensive Cardiac Remodeling by Impairing Angiogenesis
title_short Sirtuin 3 Deficiency Accelerates Hypertensive Cardiac Remodeling by Impairing Angiogenesis
title_sort sirtuin 3 deficiency accelerates hypertensive cardiac remodeling by impairing angiogenesis
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5586452/
https://www.ncbi.nlm.nih.gov/pubmed/28862956
http://dx.doi.org/10.1161/JAHA.117.006114
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