ArticleCirculation research2011
Inhibition of PKCα/β with ruboxistaurin antagonizes heart failure in pigs after myocardial infarction injury.
Article in Circulation research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 59 citations in OpenAlex.
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- The Role of PKC-MAPK Signalling Pathways in the Development of Hyperglycemia-Induced Cardiovascular Complications.International journal of molecular sciences · 2022Review
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- Scar Formation with Decreased Cardiac Function Following Ischemia/Reperfusion Injury in 1 Month Old Swine.Journal of cardiovascular development and disease · 2019Article
- Association of Regulatory Genetic Variants for Protein Kinase Cα with Mortality and Drug Efficacy in Patients with Heart Failure.Cardiovascular drugs and therapy · 2019Article
- Statin-specific inhibition of Rab-GTPase regulates cPKC-mediated IKs internalization.Scientific reports · 2019Article
- PKC and PKN in heart disease.Journal of molecular and cellular cardiology · 2019Review
- Genetic Reduction in Left Ventricular Protein Kinase C-α and Adverse Ventricular Remodeling in Human Subjects.Circulation. Genomic and precision medicine · 2018Article
- Transient activation of PKC results in long-lasting detrimental effects on systolic [CaJournal of molecular and cellular cardiology · 2018Article
- Protein Kinase C Inhibition With Ruboxistaurin Increases Contractility and Reduces Heart Size in a Swine Model of Heart Failure With Reduced Ejection Fraction.JACC. Basic to translational science · 2017Article
- Is Protein Kinase C Inhibition the Tip of the Iceberg in New Therapeutics for Acutely Decompensated Heart Failure?JACC. Basic to translational science · 2017Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
rationaleProtein kinase Cα (PKCα) activity and protein level are induced during cardiac disease where it controls myocardial contractility and propensity to heart failure in mice and rats. For example, mice lacking the gene for PKCα have enhanced cardiac contractility and reduced susceptibility to heart failure after long-term pressure overload or after myocardial infarction injury. Pharmacological inhibition of PKCα/β with Ro-32-0432, Ro-31-8220 or ruboxistaurin (LY333531) similarly enhances cardiac function and antagonizes heart failure in multiple models of disease in both mice and rats.
objectiveLarge and small mammals differ in several key indexes of heart function and biochemistry, lending uncertainty as to how PKCα/β inhibition might affect or protect a large animal model of heart failure. METHODS AND
resultsWe demonstrate that ruboxistaurin administration to a pig model of myocardial infarction-induced heart failure was protective. Twenty-kilogram pigs underwent left anterior descending artery occlusion resulting in myocardial infarctions and were then divided into vehicle or ruboxistaurin feed groups, after which they were monitored monthly for the next 3 months. Ruboxistaurin administered pigs showed significantly better recovery of myocardial contractility 3 months after infarction injury, greater ejection fraction, and greater cardiac output compared with vehicle-treated pigs.
conclusionsThese results provide additional evidence in a large animal model of disease that PKCα/β inhibition (with ruboxistaurin) represents a tenable and novel therapeutic approach for treating human heart failure.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.