FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W156315388> ?p ?o ?g. }

• W156315388 abstract "Accelerated atherosclerosis and cardiovascular disease are seen in patients with primary vasculitis (PSV) and rheumatoid arthritis (RA). The mechanisms behind this remain unclear, but recent studies have linked it to endothelial cell dysfunction (ECD), which may result from the vasculitis also seen in RA, secondary to the joint disease. TNFα has been shown to induce ECD in vitro and in vivo through poorly understood mechanisms, but other pro‐inflammatory cytokines can induce secretion of acid sphingomyelinase (ASM) from EC. ASM has been shown to induce reduced intracellular Ca(^{2+})((_i)Ca(^{2+})) signalling responses in lymphocytes through ceramide generation. Since NO production in EC is tightly coupled to agonist‐induced (_i)Ca(^{2+}) responses, this thesis set out to investigate whether inflammatory mediator‐induced secretion of ASM (S‐SMase) could regulate EC function through changes in (_i)Ca(^{2+}) responses. The activity of S‐SMase in blood from patients with RA and primary vasculitis was also assessed to underline the clinical relevance of the hypothesis. Patients (n=20) with ANCA‐associated systemic vasculitis (AASV) had high levels of S‐SMase (114.8 ± 41 pmol/mL/h(^{‐1})) in their blood compared to 13 healthy controls (52.3 ± 35 pmol/mL/h(^{‐1})). These levels fell following induction of remission by 14 weeks (96.7 ± 41 pmol/mL/h(^{‐1})) and remained low at 6 months (33.7 ± 14 pmol/mL/h(^{‐1})). Raised active blood S‐SMase was also confirmed in 35 patients with RA (84.1 ± 35 pmol/mL/h(^{‐1})) where enzyme activity correlated with several CV risk factors. TNFαdirectly induced the secretion of a redox‐sensitive and enzymatically active S‐SMase from human umbilical vein EC (HUVEC), a process blocked by antibody‐mediated inhibition of TNFα. Exposure of HUVEC to ASM inhibited (_i)Ca(^{2+}) signals in response to bradykinin. Subsequent studies on endothelial nitric oxide synthase (eNOS) suggested that exogenous ASM could alter eNOS phosphorylation at Ser(^{1177}) responsible for its activation, while ASM may also decrease NO production in HUVEC. We propose that TNFα and the prevalent oxidative environment at sites of vascular inflammation could promote increased activation and secretion of S‐SMase that would act systemically on EC causing diffuse, widespread ECD promoting the development of atherosclerosis in inflammatory disease." @default.
• W156315388 created "2016-06-24" @default.
• W156315388 creator A5003613699 @default.
• W156315388 date "2011-07-01" @default.
• W156315388 modified "2023-09-23" @default.
• W156315388 title "The effects of acid sphingomyelinase on endothelial cell function and its role in chronic inflammatory disease" @default.
• W156315388 hasPublicationYear "2011" @default.
• W156315388 type Work @default.
• W156315388 sameAs 156315388 @default.
• W156315388 citedByCount "0" @default.
• W156315388 crossrefType "dissertation" @default.
• W156315388 hasAuthorship W156315388A5003613699 @default.
• W156315388 hasConcept C126322002 @default.
• W156315388 hasConcept C134018914 @default.
• W156315388 hasConcept C142724271 @default.
• W156315388 hasConcept C150903083 @default.
• W156315388 hasConcept C164027704 @default.
• W156315388 hasConcept C17991360 @default.
• W156315388 hasConcept C185592680 @default.
• W156315388 hasConcept C190283241 @default.
• W156315388 hasConcept C203014093 @default.
• W156315388 hasConcept C204787440 @default.
• W156315388 hasConcept C207001950 @default.
• W156315388 hasConcept C2776015282 @default.
• W156315388 hasConcept C2776164576 @default.
• W156315388 hasConcept C2776268809 @default.
• W156315388 hasConcept C2776914184 @default.
• W156315388 hasConcept C2777575956 @default.
• W156315388 hasConcept C2777851122 @default.
• W156315388 hasConcept C2778163477 @default.
• W156315388 hasConcept C2779134260 @default.
• W156315388 hasConcept C2780972559 @default.
• W156315388 hasConcept C2781070647 @default.
• W156315388 hasConcept C2781457462 @default.
• W156315388 hasConcept C49039625 @default.
• W156315388 hasConcept C55493867 @default.
• W156315388 hasConcept C61322309 @default.
• W156315388 hasConcept C71924100 @default.
• W156315388 hasConcept C86803240 @default.
• W156315388 hasConceptScore W156315388C126322002 @default.
• W156315388 hasConceptScore W156315388C134018914 @default.
• W156315388 hasConceptScore W156315388C142724271 @default.
• W156315388 hasConceptScore W156315388C150903083 @default.
• W156315388 hasConceptScore W156315388C164027704 @default.
• W156315388 hasConceptScore W156315388C17991360 @default.
• W156315388 hasConceptScore W156315388C185592680 @default.
• W156315388 hasConceptScore W156315388C190283241 @default.
• W156315388 hasConceptScore W156315388C203014093 @default.
• W156315388 hasConceptScore W156315388C204787440 @default.
• W156315388 hasConceptScore W156315388C207001950 @default.
• W156315388 hasConceptScore W156315388C2776015282 @default.
• W156315388 hasConceptScore W156315388C2776164576 @default.
• W156315388 hasConceptScore W156315388C2776268809 @default.
• W156315388 hasConceptScore W156315388C2776914184 @default.
• W156315388 hasConceptScore W156315388C2777575956 @default.
• W156315388 hasConceptScore W156315388C2777851122 @default.
• W156315388 hasConceptScore W156315388C2778163477 @default.
• W156315388 hasConceptScore W156315388C2779134260 @default.
• W156315388 hasConceptScore W156315388C2780972559 @default.
• W156315388 hasConceptScore W156315388C2781070647 @default.
• W156315388 hasConceptScore W156315388C2781457462 @default.
• W156315388 hasConceptScore W156315388C49039625 @default.
• W156315388 hasConceptScore W156315388C55493867 @default.
• W156315388 hasConceptScore W156315388C61322309 @default.
• W156315388 hasConceptScore W156315388C71924100 @default.
• W156315388 hasConceptScore W156315388C86803240 @default.
• W156315388 hasLocation W1563153881 @default.
• W156315388 hasOpenAccess W156315388 @default.
• W156315388 hasPrimaryLocation W1563153881 @default.
• W156315388 hasRelatedWork W1973293334 @default.
• W156315388 hasRelatedWork W1983229253 @default.
• W156315388 hasRelatedWork W1993754429 @default.
• W156315388 hasRelatedWork W1998673289 @default.
• W156315388 hasRelatedWork W2009735510 @default.
• W156315388 hasRelatedWork W2055294386 @default.
• W156315388 hasRelatedWork W2077052793 @default.
• W156315388 hasRelatedWork W2168444413 @default.
• W156315388 hasRelatedWork W2220595253 @default.
• W156315388 hasRelatedWork W2284807533 @default.
• W156315388 hasRelatedWork W2362313035 @default.
• W156315388 hasRelatedWork W2365448869 @default.
• W156315388 hasRelatedWork W2366900732 @default.
• W156315388 hasRelatedWork W2370496745 @default.
• W156315388 hasRelatedWork W2382682093 @default.
• W156315388 hasRelatedWork W2492244587 @default.
• W156315388 hasRelatedWork W294500184 @default.
• W156315388 hasRelatedWork W348635093 @default.
• W156315388 isParatext "false" @default.
• W156315388 isRetracted "false" @default.
• W156315388 magId "156315388" @default.
• W156315388 workType "dissertation" @default.