Asset Details
Do you wish to reserve the book?
Hippo pathway deficiency reverses systolic heart failure after infarction
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Hippo pathway deficiency reverses systolic heart failure after infarction
Do you wish to request the book?
Hippo pathway deficiency reverses systolic heart failure after infarction
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Hippo pathway deficiency reverses systolic heart failure after infarction
2017
Overview
Deletion of the Hippo pathway component Salvador in mouse hearts with established ischaemic heart failure after myocardial infarction induces a reparative genetic program with increased scar border vascularity, reduced fibrosis, and recovery of pumping function.
Salvador deletion reverses heart failure
Previous work has shown that interfering with Hippo signalling during myocardial injury improves heart function in mice. Clinical outcomes of acute myocardial infarction in humans have improved as a result of better emergency care, but chronic heart failure, whereby the heart tissue undergoes pathological remodelling, remains a leading cause of death. James Martin and colleagues now show that the failing heart has a previously unrecognized capacity for repair. They show that blocking Hippo signalling can rescue established heart failure in mice. Deletion of the Hippo pathway component Salvador (Salv) or virus-mediated delivery of
Salv
short hairpin RNA when ischaemic heart failure is established can improve heart function in mice. The authors attribute the effect to the induction of a reparative genetic program, including increased expression of stress response genes and proliferative genes and preservation of mitochondrial quality control.
Mammalian organs vary widely in regenerative capacity. Poorly regenerative organs, such as the heart are particularly vulnerable to organ failure. Once established, heart failure commonly results in mortality
1
. The Hippo pathway, a kinase cascade that prevents adult cardiomyocyte proliferation and regeneration
2
, is upregulated in human heart failure. Here we show that deletion of the Hippo pathway component Salvador (Salv) in mouse hearts with established ischaemic heart failure after myocardial infarction induces a reparative genetic program with increased scar border vascularity, reduced fibrosis, and recovery of pumping function compared with controls. Using translating ribosomal affinity purification, we isolate cardiomyocyte-specific translating messenger RNA. Hippo-deficient cardiomyocytes have increased expression of proliferative genes and stress response genes, such as the mitochondrial quality control gene,
Park2
. Genetic studies indicate that
Park2
is essential for heart repair, suggesting a requirement for mitochondrial quality control in regenerating myocardium. Gene therapy with a virus encoding
Salv
short hairpin RNA improves heart function when delivered at the time of infarct or after ischaemic heart failure following myocardial infarction was established. Our findings indicate that the failing heart has a previously unrecognized reparative capacity involving more than cardiomyocyte renewal.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/44
/ 13/89
/ 14
/ 38/91
/ 42
/ 45
/ 45/90
/ 64/110
/ Animals
/ Cell Cycle Proteins - deficiency
/ Cell Cycle Proteins - genetics
/ Cell Cycle Proteins - metabolism
/ Cellular signal transduction
/ Complications and side effects
/ Failure
/ Fibrosis
/ Genes
/ Heart Failure, Systolic - etiology
/ Heart Failure, Systolic - metabolism
/ Heart Failure, Systolic - pathology
/ Heart Failure, Systolic - therapy
/ Humanities and Social Sciences
/ Humans
/ Kinases
/ letter
/ Mice
/ mRNA
/ Myocardial Infarction - complications
/ Myocardial Infarction - genetics
/ Myocardial Infarction - pathology
/ Myocytes, Cardiac - cytology
/ Myocytes, Cardiac - metabolism
/ Myocytes, Cardiac - pathology
/ Organs
/ Protein-Serine-Threonine Kinases - deficiency
/ Protein-Serine-Threonine Kinases - genetics
/ Protein-Serine-Threonine Kinases - metabolism
/ RNA
/ Science
