Matches in SemOpenAlex for { <https://semopenalex.org/work/W1987209075> ?p ?o ?g. }
Showing items 1 to 74 of
74
with 100 items per page.
- W1987209075 abstract "Blood flowing through vessels is typically a smooth process but becomes more turbulent and increases the hemodynamic shear stress at arterial curvatures or branching points and constriction sites. Such stress causes endothelial cells to become dysfunctional and induce atherosclerosis, yet the mechanism for this is unclear. A new study by Dunn et al. reports that disturbed blood flow shifts endothelial gene expression from genes that protect vessels from atherosclerosis (“atheroprotective”) to genes that promote atherosclerosis (“proatherogenic”) by altering genome-wide DNA methylation patterns. DNA methylation at the 5ʹ carbon of CG dinucleotides is a stable epigenetic modification that can regulate gene expression when it occurs at particular sites, such as promoter regions. DNA methylation has been associated with the pathogenesis of many complex diseases, but its role in atherosclerosis is understudied. In the current study, partial carotid artery ligation was used to introduce laminar blood-flow shear stress. This caused an apparently mechanosensitive regulation of DNA methyl transferase-1 (DNMT1), which is responsible for genome-wide methylation pattern changes in endothelial cells. Similar observations were also made in the lesser curvature of the aortic arch, which is naturally exposed to disturbed blood flow. Among the 11 mechanosensitive genes, five carried hypermethylated adenosine 3ʹ,5ʹ-monophosphate (cAMP) response elements at their promoters, implying that methylation at these sites can serve as a mechanosensitive switch for gene expression. Suppression of DNMT1 by means of RNA silencing or an inhibitor, 5ʹaza-2ʹdeoxycytidine (5Aza), blocked endothelial inflammation in vitro. In vivo, 5Aza treatment suppressed atherosclerotic lesion formation in both acute and chronic mouse models of atherosclerosis. The results of this study spark an interest in novel therapeutics to alter DNA methylation (epigenetics) in human atherosclerosis—a treatment avenue that is yet unexplored in this disease. J. Dunn et al ., Flow-dependent epigenetic DNA methylation regulates endothelial gene expression and atherosclerosis. J. Clin. Invest . 10.1172/JCI74792 (2014). [[Abstract]][1] [1]: http://www.jci.org/articles/view/74792" @default.
- W1987209075 created "2016-06-24" @default.
- W1987209075 creator A5027468650 @default.
- W1987209075 date "2014-06-25" @default.
- W1987209075 modified "2023-09-27" @default.
- W1987209075 title "Turbulent Times for the Atherosclerosis Epigenome" @default.
- W1987209075 doi "https://doi.org/10.1126/scitranslmed.3009597" @default.
- W1987209075 hasPublicationYear "2014" @default.
- W1987209075 type Work @default.
- W1987209075 sameAs 1987209075 @default.
- W1987209075 citedByCount "0" @default.
- W1987209075 crossrefType "journal-article" @default.
- W1987209075 hasAuthorship W1987209075A5027468650 @default.
- W1987209075 hasConcept C104317684 @default.
- W1987209075 hasConcept C105702510 @default.
- W1987209075 hasConcept C117717151 @default.
- W1987209075 hasConcept C150194340 @default.
- W1987209075 hasConcept C153911025 @default.
- W1987209075 hasConcept C170493617 @default.
- W1987209075 hasConcept C175211621 @default.
- W1987209075 hasConcept C190727270 @default.
- W1987209075 hasConcept C2776716733 @default.
- W1987209075 hasConcept C2779979206 @default.
- W1987209075 hasConcept C33288867 @default.
- W1987209075 hasConcept C4001165 @default.
- W1987209075 hasConcept C41091548 @default.
- W1987209075 hasConcept C50254741 @default.
- W1987209075 hasConcept C54355233 @default.
- W1987209075 hasConcept C86803240 @default.
- W1987209075 hasConcept C95444343 @default.
- W1987209075 hasConceptScore W1987209075C104317684 @default.
- W1987209075 hasConceptScore W1987209075C105702510 @default.
- W1987209075 hasConceptScore W1987209075C117717151 @default.
- W1987209075 hasConceptScore W1987209075C150194340 @default.
- W1987209075 hasConceptScore W1987209075C153911025 @default.
- W1987209075 hasConceptScore W1987209075C170493617 @default.
- W1987209075 hasConceptScore W1987209075C175211621 @default.
- W1987209075 hasConceptScore W1987209075C190727270 @default.
- W1987209075 hasConceptScore W1987209075C2776716733 @default.
- W1987209075 hasConceptScore W1987209075C2779979206 @default.
- W1987209075 hasConceptScore W1987209075C33288867 @default.
- W1987209075 hasConceptScore W1987209075C4001165 @default.
- W1987209075 hasConceptScore W1987209075C41091548 @default.
- W1987209075 hasConceptScore W1987209075C50254741 @default.
- W1987209075 hasConceptScore W1987209075C54355233 @default.
- W1987209075 hasConceptScore W1987209075C86803240 @default.
- W1987209075 hasConceptScore W1987209075C95444343 @default.
- W1987209075 hasLocation W19872090751 @default.
- W1987209075 hasOpenAccess W1987209075 @default.
- W1987209075 hasPrimaryLocation W19872090751 @default.
- W1987209075 hasRelatedWork W1894889351 @default.
- W1987209075 hasRelatedWork W2058433558 @default.
- W1987209075 hasRelatedWork W2069351086 @default.
- W1987209075 hasRelatedWork W2086229618 @default.
- W1987209075 hasRelatedWork W2094847578 @default.
- W1987209075 hasRelatedWork W2096994500 @default.
- W1987209075 hasRelatedWork W2123914057 @default.
- W1987209075 hasRelatedWork W2124099467 @default.
- W1987209075 hasRelatedWork W2135583284 @default.
- W1987209075 hasRelatedWork W2135825205 @default.
- W1987209075 hasRelatedWork W2137798131 @default.
- W1987209075 hasRelatedWork W2152054355 @default.
- W1987209075 hasRelatedWork W2156334465 @default.
- W1987209075 hasRelatedWork W2166283433 @default.
- W1987209075 hasRelatedWork W2518925949 @default.
- W1987209075 hasRelatedWork W2587262629 @default.
- W1987209075 hasRelatedWork W2964134329 @default.
- W1987209075 hasRelatedWork W3043723571 @default.
- W1987209075 hasRelatedWork W3083662059 @default.
- W1987209075 hasRelatedWork W75154101 @default.
- W1987209075 isParatext "false" @default.
- W1987209075 isRetracted "false" @default.
- W1987209075 magId "1987209075" @default.
- W1987209075 workType "article" @default.