Cited 109 times in
Decreased S-nitrosylation of tissue transglutaminase contributes to age-related increases in vascular stiffness
DC Field | Value | Language |
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dc.contributor.author | 오영준 | - |
dc.date.accessioned | 2015-04-23T17:17:23Z | - |
dc.date.available | 2015-04-23T17:17:23Z | - |
dc.date.issued | 2010 | - |
dc.identifier.issn | 0009-7330 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/102179 | - |
dc.description.abstract | RATIONALE: Although an age-related decrease in NO bioavailability contributes to vascular stiffness, the underlying molecular mechanisms remain incompletely understood. We hypothesize that NO constrains the activity of the matrix crosslinking enzyme tissue transglutaminase (TG2) via S-nitrosylation in young vessels, a process that is reversed in aging. OBJECTIVE: We sought to determine whether endothelium-dependent NO regulates TG2 activity by S-nitrosylation and whether this contributes to age-related vascular stiffness. METHODS AND RESULTS: We first demonstrate that NO suppresses activity and increases S-nitrosylation of TG2 in cellular models. Next, we show that nitric oxide synthase (NOS) inhibition leads to increased surface and extracellular matrix-associated TG2. We then demonstrate that endothelium-derived bioactive NO primarily mediates its effects through TG2, using TG2(-/-) mice chronically treated with the NOS inhibitor l-N(G)-nitroarginine methyl ester (L-NAME). We confirm that TG2 activity is modulated by endothelium-derived bioactive NO in young rat aorta. In aging rat aorta, although TG2 expression remains unaltered, its activity increases and S-nitrosylation decreases. Furthermore, TG2 inhibition decreases vascular stiffness in aging rats. Finally, TG2 activity and matrix crosslinks are augmented with age in human aorta, whereas abundance remains unchanged. CONCLUSIONS: Decreased S-nitrosylation of TG2 and increased TG activity lead to enhanced matrix crosslinking and contribute to vascular stiffening in aging. TG2 appears to be the member of the transglutaminase family primarily contributing to this phenotype. Inhibition of TG2 could thus represent a therapeutic target for age-associated vascular stiffness and isolated systolic hypertension. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 117~125 | - |
dc.relation.isPartOf | CIRCULATION RESEARCH | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Adult | - |
dc.subject.MESH | Age Factors | - |
dc.subject.MESH | Aged | - |
dc.subject.MESH | Aged, 80 and over | - |
dc.subject.MESH | Aging/metabolism* | - |
dc.subject.MESH | Aging/pathology | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Cells, Cultured | - |
dc.subject.MESH | Endothelium, Vascular/enzymology* | - |
dc.subject.MESH | Endothelium, Vascular/pathology | - |
dc.subject.MESH | GTP-Binding Proteins/antagonists & inhibitors | - |
dc.subject.MESH | GTP-Binding Proteins/metabolism* | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Transgenic | - |
dc.subject.MESH | Middle Aged | - |
dc.subject.MESH | NIH 3T3 Cells | - |
dc.subject.MESH | Nitric Oxide/antagonists & inhibitors | - |
dc.subject.MESH | Nitric Oxide/physiology* | - |
dc.subject.MESH | Rats | - |
dc.subject.MESH | Rats, Inbred F344 | - |
dc.subject.MESH | Transglutaminases/antagonists & inhibitors | - |
dc.subject.MESH | Transglutaminases/metabolism* | - |
dc.title | Decreased S-nitrosylation of tissue transglutaminase contributes to age-related increases in vascular stiffness | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Anesthesiology (마취통증의학) | - |
dc.contributor.googleauthor | Lakshmi Santhanam | - |
dc.contributor.googleauthor | Eric C. Tuday | - |
dc.contributor.googleauthor | Alanah K. Webb | - |
dc.contributor.googleauthor | Phillip Dowzicky | - |
dc.contributor.googleauthor | Jae Hyung Kim | - |
dc.contributor.googleauthor | Young Jun Oh | - |
dc.contributor.googleauthor | Gautam Sikka | - |
dc.contributor.googleauthor | Maggie Kuo | - |
dc.contributor.googleauthor | Marc K. Halushka | - |
dc.contributor.googleauthor | Anne M. Macgregor | - |
dc.contributor.googleauthor | Jessilyn Dunn | - |
dc.contributor.googleauthor | Sarah Gutbrod | - |
dc.contributor.googleauthor | David Yin | - |
dc.contributor.googleauthor | Artin Shoukas | - |
dc.contributor.googleauthor | Daniel Nyhan | - |
dc.contributor.googleauthor | Nicholas A. Flavahan | - |
dc.contributor.googleauthor | Alexey M. Belkin | - |
dc.contributor.googleauthor | Dan E. Berkowitz | - |
dc.identifier.doi | 10.1161/CIRCRESAHA.109.215228 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A02389 | - |
dc.relation.journalcode | J00535 | - |
dc.identifier.eissn | 1524-4571 | - |
dc.identifier.pmid | 20489165 | - |
dc.contributor.alternativeName | Oh, Young Jun | - |
dc.contributor.affiliatedAuthor | Oh, Young Jun | - |
dc.citation.volume | 107 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 117 | - |
dc.citation.endPage | 125 | - |
dc.identifier.bibliographicCitation | CIRCULATION RESEARCH, Vol.107(1) : 117-125, 2010 | - |
dc.identifier.rimsid | 50001 | - |
dc.type.rims | ART | - |
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