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Article: Vascular endothelium–targeted Sirt7 gene therapy rejuvenates blood vessels and extends life span in a Hutchinson-Gilford progeria model

TitleVascular endothelium–targeted Sirt7 gene therapy rejuvenates blood vessels and extends life span in a Hutchinson-Gilford progeria model
Authors
Issue Date2020
PublisherAmerican Association for the Advancement of Science: Science Advances. The Journal's web site is located at http://www.scienceadvances.org/
Citation
Science Advances, 2020, v. 6 n. 8, p. article no. eaay5556 How to Cite?
AbstractVascular dysfunction is a typical characteristic of aging, but its contributing roles to systemic aging and the therapeutic potential are lacking experimental evidence. Here, we generated a knock-in mouse model with the causative Hutchinson-Gilford progeria syndrome (HGPS) LmnaG609G mutation, called progerin. The Lmnaf/f;TC mice with progerin expression induced by Tie2-Cre exhibit defective microvasculature and neovascularization, accelerated aging, and shortened life span. Single-cell transcriptomic analysis of murine lung endothelial cells revealed a substantial up-regulation of inflammatory response. Molecularly, progerin interacts and destabilizes deacylase Sirt7; ectopic expression of Sirt7 alleviates the inflammatory response caused by progerin in endothelial cells. Vascular endothelium–targeted Sirt7 gene therapy, driven by an ICAM2 promoter, improves neovascularization, ameliorates aging features, and extends life span in Lmnaf/f;TC mice. These data support endothelial dysfunction as a primary trigger of systemic aging and highlight gene therapy as a potential strategy for the clinical treatment of HGPS and age-related vascular dysfunction.
Persistent Identifierhttp://hdl.handle.net/10722/294013
ISSN
2023 Impact Factor: 11.7
2023 SCImago Journal Rankings: 4.483
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSun, S-
dc.contributor.authorQin, W-
dc.contributor.authorTang, X-
dc.contributor.authorMeng, Y-
dc.contributor.authorHe, W-
dc.contributor.authorZhang, S-
dc.contributor.authorQian, M-
dc.contributor.authorLiu, Z-
dc.contributor.authorCao, X-
dc.contributor.authorPang, Q-
dc.contributor.authorZhao, B-
dc.contributor.authorWang, Z-
dc.contributor.authorZhou, Z-
dc.contributor.authorLiu, B-
dc.date.accessioned2020-11-23T08:25:07Z-
dc.date.available2020-11-23T08:25:07Z-
dc.date.issued2020-
dc.identifier.citationScience Advances, 2020, v. 6 n. 8, p. article no. eaay5556-
dc.identifier.issn2375-2548-
dc.identifier.urihttp://hdl.handle.net/10722/294013-
dc.description.abstractVascular dysfunction is a typical characteristic of aging, but its contributing roles to systemic aging and the therapeutic potential are lacking experimental evidence. Here, we generated a knock-in mouse model with the causative Hutchinson-Gilford progeria syndrome (HGPS) LmnaG609G mutation, called progerin. The Lmnaf/f;TC mice with progerin expression induced by Tie2-Cre exhibit defective microvasculature and neovascularization, accelerated aging, and shortened life span. Single-cell transcriptomic analysis of murine lung endothelial cells revealed a substantial up-regulation of inflammatory response. Molecularly, progerin interacts and destabilizes deacylase Sirt7; ectopic expression of Sirt7 alleviates the inflammatory response caused by progerin in endothelial cells. Vascular endothelium–targeted Sirt7 gene therapy, driven by an ICAM2 promoter, improves neovascularization, ameliorates aging features, and extends life span in Lmnaf/f;TC mice. These data support endothelial dysfunction as a primary trigger of systemic aging and highlight gene therapy as a potential strategy for the clinical treatment of HGPS and age-related vascular dysfunction.-
dc.languageeng-
dc.publisherAmerican Association for the Advancement of Science: Science Advances. The Journal's web site is located at http://www.scienceadvances.org/-
dc.relation.ispartofScience Advances-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleVascular endothelium–targeted Sirt7 gene therapy rejuvenates blood vessels and extends life span in a Hutchinson-Gilford progeria model-
dc.typeArticle-
dc.identifier.emailZhou, Z: zhongjun@hku.hk-
dc.identifier.authorityZhou, Z=rp00503-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1126/sciadv.aay5556-
dc.identifier.pmid32128409-
dc.identifier.pmcidPMC7030934-
dc.identifier.scopuseid_2-s2.0-85079606332-
dc.identifier.hkuros319257-
dc.identifier.volume6-
dc.identifier.issue8-
dc.identifier.spagearticle no. eaay5556-
dc.identifier.epagearticle no. eaay5556-
dc.identifier.isiWOS:000514842000023-
dc.publisher.placeUnited States-

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