FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2022379266> ?p ?o ?g. }

• W2022379266 endingPage "2041" @default.
• W2022379266 startingPage "2034" @default.
• W2022379266 abstract "BACKGROUND Cardiovascular disease is a leading cause of death worldwide. Arrhythmias are associated with significant morbidity and mortality related to cardiovascular disease. Recent work illustrates that many cardiac arrhythmias are initiated by a pathologic imbalance between kinase and phosphatase activities in excitable cardiomyocytes. OBJECTIVE To test the relationship between myocyte kinase/phosphatase imbalance and cellular and whole animal arrhythmia phenotypes associated with ankyrin-B cardiac syndrome. METHODS By using a combination of biochemical, electrophysiological, and in vivo approaches, we tested the ability of calcium/calmodulin-dependent kinase (CaMKII) inhibition to rescue imbalance in kinase/phosphatase pathways associated with human ankyrin-B-associated cardiac arrhythmia. RESULTS The cardiac ryanodine receptor (RyR2), a validated target of kinase/phosphatase regulation in myocytes, displays abnormal CaMKII-dependent phosphorylation (pS2814 hyperphosphorylation) in ankyrin-B+/− heart. Notably, RyR2 dysregulation is rescued in myocytes from ankyrin-B+/− mice overexpressing a potent CaMKII-inhibitory peptide (AC3I), and aberrant RyR2 open probability observed in ankyrin-B+/− hearts is normalized by treatment with the CaMKII inhibitor KN-93. CaMKII inhibition is sufficient to rescue abnormalities in ankyrin-B+/− myocyte electrical dysfunction including cellular afterdepolarizations, and significantly blunts whole animal cardiac arrhythmias and sudden death in response to elevated sympathetic tone. CONCLUSIONS These findings illustrate the complexity of the molecular components involved in human arrhythmia and define regulatory elements of the ankyrin-B pathway in pathophysiology. Furthermore, the findings illustrate the potential impact of CaMKII inhibition in the treatment of a congenital form of human cardiac arrhythmia. Cardiovascular disease is a leading cause of death worldwide. Arrhythmias are associated with significant morbidity and mortality related to cardiovascular disease. Recent work illustrates that many cardiac arrhythmias are initiated by a pathologic imbalance between kinase and phosphatase activities in excitable cardiomyocytes. To test the relationship between myocyte kinase/phosphatase imbalance and cellular and whole animal arrhythmia phenotypes associated with ankyrin-B cardiac syndrome. By using a combination of biochemical, electrophysiological, and in vivo approaches, we tested the ability of calcium/calmodulin-dependent kinase (CaMKII) inhibition to rescue imbalance in kinase/phosphatase pathways associated with human ankyrin-B-associated cardiac arrhythmia. The cardiac ryanodine receptor (RyR2), a validated target of kinase/phosphatase regulation in myocytes, displays abnormal CaMKII-dependent phosphorylation (pS2814 hyperphosphorylation) in ankyrin-B+/− heart. Notably, RyR2 dysregulation is rescued in myocytes from ankyrin-B+/− mice overexpressing a potent CaMKII-inhibitory peptide (AC3I), and aberrant RyR2 open probability observed in ankyrin-B+/− hearts is normalized by treatment with the CaMKII inhibitor KN-93. CaMKII inhibition is sufficient to rescue abnormalities in ankyrin-B+/− myocyte electrical dysfunction including cellular afterdepolarizations, and significantly blunts whole animal cardiac arrhythmias and sudden death in response to elevated sympathetic tone. These findings illustrate the complexity of the molecular components involved in human arrhythmia and define regulatory elements of the ankyrin-B pathway in pathophysiology. Furthermore, the findings illustrate the potential impact of CaMKII inhibition in the treatment of a congenital form of human cardiac arrhythmia." @default.
• W2022379266 created "2016-06-24" @default.
• W2022379266 creator A5000609088 @default.
• W2022379266 creator A5002379831 @default.
• W2022379266 creator A5020237757 @default.
• W2022379266 creator A5021749666 @default.
• W2022379266 creator A5026176616 @default.
• W2022379266 creator A5031315906 @default.
• W2022379266 creator A5046562663 @default.
• W2022379266 creator A5048118890 @default.
• W2022379266 creator A5067437780 @default.
• W2022379266 creator A5067955997 @default.
• W2022379266 creator A5073506761 @default.
• W2022379266 creator A5076237679 @default.
• W2022379266 creator A5081274351 @default.
• W2022379266 date "2012-12-01" @default.
• W2022379266 modified "2023-09-27" @default.
• W2022379266 title "CaMKII inhibition rescues proarrhythmic phenotypes in the model of human ankyrin-B syndrome" @default.
• W2022379266 cites W1492909811 @default.
• W2022379266 cites W1969961716 @default.
• W2022379266 cites W1971203163 @default.
• W2022379266 cites W1986033460 @default.
• W2022379266 cites W1986652655 @default.
• W2022379266 cites W1996156433 @default.
• W2022379266 cites W1996439106 @default.
• W2022379266 cites W2001261561 @default.
• W2022379266 cites W2012531906 @default.
• W2022379266 cites W2014843536 @default.
• W2022379266 cites W2051461374 @default.
• W2022379266 cites W2060046353 @default.
• W2022379266 cites W2061686154 @default.
• W2022379266 cites W2064924372 @default.
• W2022379266 cites W2067307702 @default.
• W2022379266 cites W2080397790 @default.
• W2022379266 cites W2091133442 @default.
• W2022379266 cites W2096875864 @default.
• W2022379266 cites W2097312037 @default.
• W2022379266 cites W2103154455 @default.
• W2022379266 cites W2108376995 @default.
• W2022379266 cites W2108608061 @default.
• W2022379266 cites W2111088142 @default.
• W2022379266 cites W2115923216 @default.
• W2022379266 cites W2116297568 @default.
• W2022379266 cites W2119084059 @default.
• W2022379266 cites W2120618651 @default.
• W2022379266 cites W2132622900 @default.
• W2022379266 cites W2133444462 @default.
• W2022379266 cites W2134798732 @default.
• W2022379266 cites W2135576636 @default.
• W2022379266 cites W2138387305 @default.
• W2022379266 cites W2141823911 @default.
• W2022379266 cites W2147343486 @default.
• W2022379266 cites W2151702576 @default.
• W2022379266 cites W2155116390 @default.
• W2022379266 cites W2165525914 @default.
• W2022379266 cites W2166533036 @default.
• W2022379266 cites W2337068216 @default.
• W2022379266 doi "https://doi.org/10.1016/j.hrthm.2012.08.026" @default.
• W2022379266 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3630478" @default.
• W2022379266 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23059182" @default.
• W2022379266 hasPublicationYear "2012" @default.
• W2022379266 type Work @default.
• W2022379266 sameAs 2022379266 @default.
• W2022379266 citedByCount "40" @default.
• W2022379266 countsByYear W20223792662012 @default.
• W2022379266 countsByYear W20223792662013 @default.
• W2022379266 countsByYear W20223792662014 @default.
• W2022379266 countsByYear W20223792662015 @default.
• W2022379266 countsByYear W20223792662016 @default.
• W2022379266 countsByYear W20223792662017 @default.
• W2022379266 countsByYear W20223792662018 @default.
• W2022379266 countsByYear W20223792662019 @default.
• W2022379266 countsByYear W20223792662020 @default.
• W2022379266 countsByYear W20223792662022 @default.
• W2022379266 countsByYear W20223792662023 @default.
• W2022379266 crossrefType "journal-article" @default.
• W2022379266 hasAuthorship W2022379266A5000609088 @default.
• W2022379266 hasAuthorship W2022379266A5002379831 @default.
• W2022379266 hasAuthorship W2022379266A5020237757 @default.
• W2022379266 hasAuthorship W2022379266A5021749666 @default.
• W2022379266 hasAuthorship W2022379266A5026176616 @default.
• W2022379266 hasAuthorship W2022379266A5031315906 @default.
• W2022379266 hasAuthorship W2022379266A5046562663 @default.
• W2022379266 hasAuthorship W2022379266A5048118890 @default.
• W2022379266 hasAuthorship W2022379266A5067437780 @default.
• W2022379266 hasAuthorship W2022379266A5067955997 @default.
• W2022379266 hasAuthorship W2022379266A5073506761 @default.
• W2022379266 hasAuthorship W2022379266A5076237679 @default.
• W2022379266 hasAuthorship W2022379266A5081274351 @default.
• W2022379266 hasBestOaLocation W20223792662 @default.
• W2022379266 hasConcept C104317684 @default.
• W2022379266 hasConcept C113217602 @default.
• W2022379266 hasConcept C126322002 @default.
• W2022379266 hasConcept C134018914 @default.
• W2022379266 hasConcept C170493617 @default.
• W2022379266 hasConcept C182800266 @default.
• W2022379266 hasConcept C190712762 @default.
• W2022379266 hasConcept C207200792 @default.

• next