2019
PDE1 inhibition facilitates proteasomal degradation of misfolded proteins and protects against cardiac proteinopathy
Zhang H, Pan B, Wu P, Parajuli N, Rekhter MD, Goldberg AL, Wang X. PDE1 inhibition facilitates proteasomal degradation of misfolded proteins and protects against cardiac proteinopathy. Science Advances 2019, 5: eaaw5870. PMID: 31131329, PMCID: PMC6531002, DOI: 10.1126/sciadv.aaw5870.Peer-Reviewed Original ResearchMeSH KeywordsAlpha-Crystallin B ChainAnimalsCyclic AMP-Dependent Protein KinasesCyclic GMP-Dependent Protein KinasesCyclic Nucleotide Phosphodiesterases, Type 1DensitometryEchocardiographyFemaleGenotypeHeart FailureHeart VentriclesHemodynamicsHumansHydrolysisMaleMiceMice, TransgenicMicroscopy, FluorescenceMyocytes, CardiacPhosphorylationProteasome Endopeptidase ComplexProtein DenaturationProtein FoldingProteostasis DeficienciesRats
2018
Inhibition of Type 1 Phosphodiesterse Confers Therapeutic Benefit to Proteinopathy‐based HFpEF in Mice
Zhang H, Rekhter M, Wang X. Inhibition of Type 1 Phosphodiesterse Confers Therapeutic Benefit to Proteinopathy‐based HFpEF in Mice. The FASEB Journal 2018, 32: 903.14-903.14. DOI: 10.1096/fasebj.2018.32.1_supplement.903.14.Peer-Reviewed Original ResearchCardiac ubiquitin-proteasome systemProtein kinase GHeart failureEjection fractionTg micePDE1 inhibitionTherapeutic strategiesUbiquitin-proteasome systemLeft ventricular end-diastolic volumeVentricular end-diastolic volumeKaplan-Meier survival analysisInhibition groupNon-Tg miceLV posterior wallProtein kinase AEnd-diastolic volumeHeart failure casesTreatment of HFPotential therapeutic strategyNew therapeutic strategiesMonths of ageFull-text articlesInsufficiency contributesMortality benefitPharmacological therapy
2015
Priming the proteasome by protein kinase G: a novel cardioprotective mechanism of sildenafil
Zhang H, Wang X. Priming the proteasome by protein kinase G: a novel cardioprotective mechanism of sildenafil. Future Cardiology 2015, 11: 177-189. PMID: 25760877, PMCID: PMC4370174, DOI: 10.2217/fca.15.3.Peer-Reviewed Original ResearchConceptsProtein kinase GProtein quality controlMost cellular proteinsKinase GNovel cardioprotective mechanismProteasome enhancementCardiac protein quality controlProtein kinase G activationMisfolded proteinsProtein hemostasisCellular proteinsProteasomal degradationCardiac proteinopathyHuman failing heartsProteinProteasomeNew therapeutic strategiesG activationTherapeutic strategiesMajor pathogenic factorFunctional insufficiencyCardioprotective mechanismsLarge subsetDegradationMechanism