FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1966557197> ?p ?o ?g. }

• W1966557197 endingPage "444" @default.
• W1966557197 startingPage "436" @default.
• W1966557197 abstract "Background— Low activity of the sarco(endo)plasmic reticulum Ca 2+ -ATPase (SERCA2a) resulting from strong inhibition by phospholamban (PLN) can depress cardiac contractility and lead to dilated cardiomyopathy and heart failure. Here, we investigated whether PLN exhibits cardiotoxic effects via mechanisms other than chronic inhibition of SERCA2a by studying a PLN mutant, PLN R9C , that triggers cardiac failure in humans and mice. Methods and Results— Because PLN R9C inhibits SERCA2a mainly by preventing deactivation of wild-type PLN, SERCA2a activity could be increased stepwise by generating mice that carry a PLN R9C transgene and 2, 1, or 0 endogenous PLN alleles (PLN +/+ +TgPLN R9C , PLN +/− +TgPLN R9C , and PLN −/− +TgPLN R9C , respectively). PLN −/− +TgPLN R9C hearts demonstrated accelerated sarcoplasmic reticulum Ca 2+ uptake rates and improved hemodynamics compared with PLN +/+ +TgPLN R9C mice but still responded poorly to β-adrenergic stimulation because PLN R9C impairs protein kinase A–mediated phosphorylation of both wild-type and mutant PLN. PLN +/+ +TgPLN R9C mice died of heart failure at 21±6 weeks, whereas heterozygous PLN +/− +TgPLN R9C mice survived to 48±11 weeks, PLN −/− +TgPLN R9C mice to 66±19 weeks, and wild-type mice to 94±27 weeks ( P <0.001). Although Ca 2+ reuptake kinetics in young PLN −/− +TgPLN R9C mice exceeded those measured in wild-type control animals, this parameter alone was not sufficient to prevent the eventual development of dilated cardiomyopathy. Conclusions— The data demonstrate an association between the dose-dependent inhibition of SERCA2a activity by PLN wt and the time of onset of heart failure and show that a weak inhibitor of SERCA2a, PLN R9C , which is diminished in its ability to modify the level of SERCA2a activity, leads to heart failure despite fast sarcoplasmic reticulum Ca 2+ reuptake." @default.
• W1966557197 created "2016-06-24" @default.
• W1966557197 creator A5003703339 @default.
• W1966557197 creator A5005091829 @default.
• W1966557197 creator A5019869416 @default.
• W1966557197 creator A5048869732 @default.
• W1966557197 creator A5051535283 @default.
• W1966557197 creator A5066595684 @default.
• W1966557197 creator A5068839871 @default.
• W1966557197 creator A5077830375 @default.
• W1966557197 creator A5085011132 @default.
• W1966557197 creator A5088154202 @default.
• W1966557197 date "2009-01-27" @default.
• W1966557197 modified "2023-10-18" @default.
• W1966557197 title "Alterations of Phospholamban Function Can Exhibit Cardiotoxic Effects Independent of Excessive Sarcoplasmic Reticulum Ca ²⁺ -ATPase Inhibition" @default.
• W1966557197 cites W1539099740 @default.
• W1966557197 cites W1546299041 @default.
• W1966557197 cites W1999215577 @default.
• W1966557197 cites W2026182775 @default.
• W1966557197 cites W2045143786 @default.
• W1966557197 cites W2048867275 @default.
• W1966557197 cites W2064705407 @default.
• W1966557197 cites W2074137489 @default.
• W1966557197 cites W2079697827 @default.
• W1966557197 cites W2094074899 @default.
• W1966557197 cites W2109123990 @default.
• W1966557197 cites W2109331497 @default.
• W1966557197 cites W2114942701 @default.
• W1966557197 cites W2115032762 @default.
• W1966557197 cites W2115638751 @default.
• W1966557197 cites W2157887741 @default.
• W1966557197 cites W2164624052 @default.
• W1966557197 cites W2242453161 @default.
• W1966557197 cites W4244420109 @default.
• W1966557197 doi "https://doi.org/10.1161/circulationaha.108.783506" @default.
• W1966557197 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19139388" @default.
• W1966557197 hasPublicationYear "2009" @default.
• W1966557197 type Work @default.
• W1966557197 sameAs 1966557197 @default.
• W1966557197 citedByCount "44" @default.
• W1966557197 countsByYear W19665571972012 @default.
• W1966557197 countsByYear W19665571972014 @default.
• W1966557197 countsByYear W19665571972015 @default.
• W1966557197 countsByYear W19665571972016 @default.
• W1966557197 countsByYear W19665571972017 @default.
• W1966557197 countsByYear W19665571972018 @default.
• W1966557197 countsByYear W19665571972019 @default.
• W1966557197 countsByYear W19665571972020 @default.
• W1966557197 countsByYear W19665571972021 @default.
• W1966557197 countsByYear W19665571972022 @default.
• W1966557197 countsByYear W19665571972023 @default.
• W1966557197 crossrefType "journal-article" @default.
• W1966557197 hasAuthorship W1966557197A5003703339 @default.
• W1966557197 hasAuthorship W1966557197A5005091829 @default.
• W1966557197 hasAuthorship W1966557197A5019869416 @default.
• W1966557197 hasAuthorship W1966557197A5048869732 @default.
• W1966557197 hasAuthorship W1966557197A5051535283 @default.
• W1966557197 hasAuthorship W1966557197A5066595684 @default.
• W1966557197 hasAuthorship W1966557197A5068839871 @default.
• W1966557197 hasAuthorship W1966557197A5077830375 @default.
• W1966557197 hasAuthorship W1966557197A5085011132 @default.
• W1966557197 hasAuthorship W1966557197A5088154202 @default.
• W1966557197 hasBestOaLocation W19665571971 @default.
• W1966557197 hasConcept C104317684 @default.
• W1966557197 hasConcept C111566952 @default.
• W1966557197 hasConcept C11960822 @default.
• W1966557197 hasConcept C126322002 @default.
• W1966557197 hasConcept C134018914 @default.
• W1966557197 hasConcept C143065580 @default.
• W1966557197 hasConcept C158617107 @default.
• W1966557197 hasConcept C17137333 @default.
• W1966557197 hasConcept C181199279 @default.
• W1966557197 hasConcept C207583985 @default.
• W1966557197 hasConcept C23265538 @default.
• W1966557197 hasConcept C2776383484 @default.
• W1966557197 hasConcept C2778198053 @default.
• W1966557197 hasConcept C2778797674 @default.
• W1966557197 hasConcept C2781414619 @default.
• W1966557197 hasConcept C39133596 @default.
• W1966557197 hasConcept C55493867 @default.
• W1966557197 hasConcept C71924100 @default.
• W1966557197 hasConcept C86803240 @default.
• W1966557197 hasConcept C95444343 @default.
• W1966557197 hasConcept C98274493 @default.
• W1966557197 hasConceptScore W1966557197C104317684 @default.
• W1966557197 hasConceptScore W1966557197C111566952 @default.
• W1966557197 hasConceptScore W1966557197C11960822 @default.
• W1966557197 hasConceptScore W1966557197C126322002 @default.
• W1966557197 hasConceptScore W1966557197C134018914 @default.
• W1966557197 hasConceptScore W1966557197C143065580 @default.
• W1966557197 hasConceptScore W1966557197C158617107 @default.
• W1966557197 hasConceptScore W1966557197C17137333 @default.
• W1966557197 hasConceptScore W1966557197C181199279 @default.
• W1966557197 hasConceptScore W1966557197C207583985 @default.
• W1966557197 hasConceptScore W1966557197C23265538 @default.
• W1966557197 hasConceptScore W1966557197C2776383484 @default.
• W1966557197 hasConceptScore W1966557197C2778198053 @default.
• W1966557197 hasConceptScore W1966557197C2778797674 @default.

• next