FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2733377210> ?p ?o ?g. }

• W2733377210 endingPage "1417" @default.
• W2733377210 startingPage "1403" @default.
• W2733377210 abstract "The histidine-rich calcium-binding protein (HRC) Ser96Ala variant has previously been identified as a potential biomarker for ventricular arrhythmias and sudden cardiac death in patients with idiopathic dilated cardiomyopathy. Herein, the role of this variant in cardiac pathophysiology is delineated through a novel mouse model, carrying the human mutation in the homologous mouse position.The mouse HRC serine 81, homologous to human HRC serine 96, was mutated to alanine, using knock-in gene targeting. The HRC-Ser81Ala mice presented increased mortality in the absence of structural or histological abnormalities, indicating that early death may be arrhythmia-related. Indeed, under stress-but not baseline-conditions, the HRC-Ser81Ala mice developed ventricular arrhythmias, whilst at the cardiomyocyte level they exhibited increased occurrence of triggered activity. Cardiac contraction was decreased in vivo, ex vivo, and in vitro. Additionally, Ca2+ transients and SR Ca2+ load were both reduced suggesting that cytosolic Ca2+ overload is not the underlying proarrhythmic mechanism. Interestingly, total SR Ca2+ leak was increased in HRC-Ser81Ala cardiomyocytes, without an increase in Ca2+ spark and wave frequency. However, Ca2+ wave propagation was significantly slower and the duration of the associated Na/Ca exchange current was increased. Moreover, action potential duration was also increased. Notably, Ca2+/Calmodulin kinase II (CaMKII) phosphorylation of the ryanodine receptor was increased, whilst KN-93, an inhibitor of CaMKII, reduced the occurrence of arrhythmias.The homologous mutation Ser81Ala in HRC in mice, corresponding to Ser96Ala in humans, is associated with sudden death and depressed cardiac function. Ventricular arrhythmias are related to abnormal Ca2+ cycling across the SR. The data further support a role for CaMKII with the perspective to treat arrhythmias through CaMKII inhibition." @default.
• W2733377210 created "2017-07-14" @default.
• W2733377210 creator A5013447402 @default.
• W2733377210 creator A5020658595 @default.
• W2733377210 creator A5026292295 @default.
• W2733377210 creator A5034292648 @default.
• W2733377210 creator A5039759348 @default.
• W2733377210 creator A5042788376 @default.
• W2733377210 creator A5050797463 @default.
• W2733377210 creator A5059841903 @default.
• W2733377210 creator A5062733088 @default.
• W2733377210 creator A5064444514 @default.
• W2733377210 creator A5068792421 @default.
• W2733377210 creator A5074050667 @default.
• W2733377210 creator A5075657974 @default.
• W2733377210 creator A5080329479 @default.
• W2733377210 creator A5080549070 @default.
• W2733377210 creator A5083208338 @default.
• W2733377210 creator A5088538509 @default.
• W2733377210 date "2017-07-01" @default.
• W2733377210 modified "2023-10-14" @default.
• W2733377210 title "Impaired calcium homeostasis is associated with sudden cardiac death and arrhythmias in a genetic equivalent mouse model of the human HRC-Ser96Ala variant" @default.
• W2733377210 cites W1967193849 @default.
• W2733377210 cites W1971048452 @default.
• W2733377210 cites W1980830162 @default.
• W2733377210 cites W1984417539 @default.
• W2733377210 cites W1987781080 @default.
• W2733377210 cites W2005766827 @default.
• W2733377210 cites W2009708010 @default.
• W2733377210 cites W2026296218 @default.
• W2733377210 cites W2031424060 @default.
• W2733377210 cites W2033608440 @default.
• W2733377210 cites W2044227913 @default.
• W2733377210 cites W2048424360 @default.
• W2733377210 cites W2050824263 @default.
• W2733377210 cites W2051461374 @default.
• W2733377210 cites W2053330560 @default.
• W2733377210 cites W2053387749 @default.
• W2733377210 cites W2056493589 @default.
• W2733377210 cites W2064948042 @default.
• W2733377210 cites W2072775743 @default.
• W2733377210 cites W2074777877 @default.
• W2733377210 cites W2079974543 @default.
• W2733377210 cites W2081524260 @default.
• W2733377210 cites W2095077534 @default.
• W2733377210 cites W2096555186 @default.
• W2733377210 cites W2105195825 @default.
• W2733377210 cites W2108084196 @default.
• W2733377210 cites W2108670042 @default.
• W2733377210 cites W2114329647 @default.
• W2733377210 cites W2115638751 @default.
• W2733377210 cites W2116297568 @default.
• W2733377210 cites W2119129185 @default.
• W2733377210 cites W2147419988 @default.
• W2733377210 cites W2155116390 @default.
• W2733377210 cites W2158714558 @default.
• W2733377210 cites W2163547302 @default.
• W2733377210 cites W2164327283 @default.
• W2733377210 cites W2167646683 @default.
• W2733377210 cites W2168275634 @default.
• W2733377210 cites W2168841938 @default.
• W2733377210 cites W2172169253 @default.
• W2733377210 cites W2485549527 @default.
• W2733377210 cites W255523588 @default.
• W2733377210 cites W2792980560 @default.
• W2733377210 doi "https://doi.org/10.1093/cvr/cvx113" @default.
• W2733377210 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28859293" @default.
• W2733377210 hasPublicationYear "2017" @default.
• W2733377210 type Work @default.
• W2733377210 sameAs 2733377210 @default.
• W2733377210 citedByCount "11" @default.
• W2733377210 countsByYear W27333772102018 @default.
• W2733377210 countsByYear W27333772102020 @default.
• W2733377210 countsByYear W27333772102021 @default.
• W2733377210 countsByYear W27333772102023 @default.
• W2733377210 crossrefType "journal-article" @default.
• W2733377210 hasAuthorship W2733377210A5013447402 @default.
• W2733377210 hasAuthorship W2733377210A5020658595 @default.
• W2733377210 hasAuthorship W2733377210A5026292295 @default.
• W2733377210 hasAuthorship W2733377210A5034292648 @default.
• W2733377210 hasAuthorship W2733377210A5039759348 @default.
• W2733377210 hasAuthorship W2733377210A5042788376 @default.
• W2733377210 hasAuthorship W2733377210A5050797463 @default.
• W2733377210 hasAuthorship W2733377210A5059841903 @default.
• W2733377210 hasAuthorship W2733377210A5062733088 @default.
• W2733377210 hasAuthorship W2733377210A5064444514 @default.
• W2733377210 hasAuthorship W2733377210A5068792421 @default.
• W2733377210 hasAuthorship W2733377210A5074050667 @default.
• W2733377210 hasAuthorship W2733377210A5075657974 @default.
• W2733377210 hasAuthorship W2733377210A5080329479 @default.
• W2733377210 hasAuthorship W2733377210A5080549070 @default.
• W2733377210 hasAuthorship W2733377210A5083208338 @default.
• W2733377210 hasAuthorship W2733377210A5088538509 @default.
• W2733377210 hasBestOaLocation W27333772102 @default.
• W2733377210 hasConcept C113217602 @default.
• W2733377210 hasConcept C126322002 @default.
• W2733377210 hasConcept C134018914 @default.
• W2733377210 hasConcept C190712762 @default.

• next