Matches in SemOpenAlex for { <https://semopenalex.org/work/W3170376697> ?p ?o ?g. }
Showing items 1 to 60 of
60
with 100 items per page.
- W3170376697 abstract "Background and Objective Heart failure is the leading cause of death in the world. Adenylyl cyclase, that catalyzes the formation of cAMP from ATP, regulates many aspects of cardiac physiology and pathology. Klotho deficiency causes heart failure in Kotho-hypomorphic mutant (KL (-/-)) mice. The objective of this study was to investigate whether in vivo cardiac-specific adenylyl cyclase type 4 (AC4) gene expression protects against Klotho deficiency- induced heart failure. Methods and Results We found that Klotho deficiency-induced heart failure was accompanied by AC4 reduction. Next, we constructed a rAAV vector in which the truncated αMHC promoter drives the expression of AC4 (AAV2/9-αMHC-AC4). The AAV viral particles were then administered intravenously via the tail vein and the mice were sacrificed at 7 weeks after gene delivery. Interestingly, cardiac-specific AC4 gene delivery increased left ventricular fractional shortening, ejection fraction, stroke volume, and left ventricular end-diastolic volume, suggesting that cardiac-specific AC4 gene delivery protected against Klotho deficiency-induced heart dysfunction. Meanwhile, cardiac-specific AC4 gene delivery also decreased heart weight to body weight ratio and cardiomyocyte cross-section area, suggesting that cardiac-specific AC4 gene expression protected against Klotho deficiency-induced cardiac hypertrophy. Cardiac-specific AC4 gene delivery also alleviated Klotho deficiency-induced cardiac fibrosis and calcification. Furthermore, cardiac-specific AC4 gene delivery attenuated cardiomyocyte apoptotic cell death and mitochondrial dysfunction. Mechanistically, AAV2/9-αMHC-AC4 increased cardiomyocytic cAMP levels and so regulated PKA-PLN-SERCA2 signal pathway, which are critical in modulating calcium flux, mitochondrial function. Conclusion Cardiac-specific AC4 gene delivery protected against Klotho deficiency-induced heart failure through increasing cardiomyocytic cAMP levels, which alleviated PKA-dependent mitochondrial dysfunction and apoptotic cell death. AC4 could be a potential therapeutic target for heart failure associated with Klotho deficiency in aging or chronic kidney disease." @default.
- W3170376697 created "2021-06-22" @default.
- W3170376697 creator A5029679885 @default.
- W3170376697 creator A5041217714 @default.
- W3170376697 creator A5074339191 @default.
- W3170376697 date "2021-05-01" @default.
- W3170376697 modified "2023-09-25" @default.
- W3170376697 title "In Vivo Cardiac‐specific Adenylyl Cyclase 4 gene delivery protects against Klotho deficiency‐induced heart failure" @default.
- W3170376697 doi "https://doi.org/10.1096/fasebj.2021.35.s1.03337" @default.
- W3170376697 hasPublicationYear "2021" @default.
- W3170376697 type Work @default.
- W3170376697 sameAs 3170376697 @default.
- W3170376697 citedByCount "0" @default.
- W3170376697 crossrefType "journal-article" @default.
- W3170376697 hasAuthorship W3170376697A5029679885 @default.
- W3170376697 hasAuthorship W3170376697A5041217714 @default.
- W3170376697 hasAuthorship W3170376697A5074339191 @default.
- W3170376697 hasConcept C111566952 @default.
- W3170376697 hasConcept C126322002 @default.
- W3170376697 hasConcept C134018914 @default.
- W3170376697 hasConcept C24998067 @default.
- W3170376697 hasConcept C2777099384 @default.
- W3170376697 hasConcept C2778198053 @default.
- W3170376697 hasConcept C2779178603 @default.
- W3170376697 hasConcept C2780091579 @default.
- W3170376697 hasConcept C71924100 @default.
- W3170376697 hasConcept C78085059 @default.
- W3170376697 hasConcept C86803240 @default.
- W3170376697 hasConcept C9832595 @default.
- W3170376697 hasConceptScore W3170376697C111566952 @default.
- W3170376697 hasConceptScore W3170376697C126322002 @default.
- W3170376697 hasConceptScore W3170376697C134018914 @default.
- W3170376697 hasConceptScore W3170376697C24998067 @default.
- W3170376697 hasConceptScore W3170376697C2777099384 @default.
- W3170376697 hasConceptScore W3170376697C2778198053 @default.
- W3170376697 hasConceptScore W3170376697C2779178603 @default.
- W3170376697 hasConceptScore W3170376697C2780091579 @default.
- W3170376697 hasConceptScore W3170376697C71924100 @default.
- W3170376697 hasConceptScore W3170376697C78085059 @default.
- W3170376697 hasConceptScore W3170376697C86803240 @default.
- W3170376697 hasConceptScore W3170376697C9832595 @default.
- W3170376697 hasIssue "S1" @default.
- W3170376697 hasLocation W31703766971 @default.
- W3170376697 hasOpenAccess W3170376697 @default.
- W3170376697 hasPrimaryLocation W31703766971 @default.
- W3170376697 hasRelatedWork W1883738259 @default.
- W3170376697 hasRelatedWork W1986238933 @default.
- W3170376697 hasRelatedWork W2072050797 @default.
- W3170376697 hasRelatedWork W2196918288 @default.
- W3170376697 hasRelatedWork W2347245660 @default.
- W3170376697 hasRelatedWork W2887583208 @default.
- W3170376697 hasRelatedWork W3128227176 @default.
- W3170376697 hasRelatedWork W4226263639 @default.
- W3170376697 hasRelatedWork W4238889529 @default.
- W3170376697 hasRelatedWork W4240119435 @default.
- W3170376697 hasVolume "35" @default.
- W3170376697 isParatext "false" @default.
- W3170376697 isRetracted "false" @default.
- W3170376697 magId "3170376697" @default.
- W3170376697 workType "article" @default.