2021
Increased complement activation is a distinctive feature of severe SARS-CoV-2 infection
Ma L, Sahu S, Cano M, Kuppuswamy V, Bajwa J, McPhatter J, Pine A, Meizlish M, Goshua G, Chang C, Zhang H, Price C, Bahel P, Rinder H, Lei T, Day A, Reynolds D, Wu X, Schriefer R, Rauseo A, Goss C, O’Halloran J, Presti R, Kim A, Gelman A, Dela Cruz C, Lee A, Mudd P, Chun H, Atkinson J, Kulkarni H. Increased complement activation is a distinctive feature of severe SARS-CoV-2 infection. Science Immunology 2021, 6: eabh2259. PMID: 34446527, PMCID: PMC8158979, DOI: 10.1126/sciimmunol.abh2259.Peer-Reviewed Original ResearchConceptsSevere SARS-CoV-2 infectionSARS-CoV-2 infectionIntensive care unitComplement activationRespiratory failureEndothelial injuryCOVID-19Non-COVID cohortPersonalized clinical trialsAcute respiratory failureInvasive mechanical ventilationSevere COVID-19Tertiary care centerAlternative complement pathwayICU admissionCritical illnessCare unitMechanical ventilationRisk prognosticationWashington University SchoolWorse outcomesCare centerClinical trialsHigh riskPatientsPRO-THROMBOTIC SIGNATURE FROM NEUTROPHIL ACTIVATION AND DECREASED ADAMTS13 TO VWF RATIO IS A KEY DRIVER OF CARDIAC INJURY IN HOSPITALIZED PATIENTS WITH COVID-19
Wang S, Pine A, Mankbadi M, Chang C, Madeeva D, Zhang H, Dajani A, Crandall I, Sugeng L, Lee A, Chun H. PRO-THROMBOTIC SIGNATURE FROM NEUTROPHIL ACTIVATION AND DECREASED ADAMTS13 TO VWF RATIO IS A KEY DRIVER OF CARDIAC INJURY IN HOSPITALIZED PATIENTS WITH COVID-19. Journal Of The American College Of Cardiology 2021, 77: 3193. PMID: 34167644, PMCID: PMC8091195, DOI: 10.1016/s0735-1097(21)04548-4.Peer-Reviewed Original ResearchA neutrophil activation signature predicts critical illness and mortality in COVID-19
Meizlish ML, Pine AB, Bishai JD, Goshua G, Nadelmann ER, Simonov M, Chang CH, Zhang H, Shallow M, Bahel P, Owusu K, Yamamoto Y, Arora T, Atri DS, Patel A, Gbyli R, Kwan J, Won CH, Dela Cruz C, Price C, Koff J, King BA, Rinder HM, Wilson FP, Hwa J, Halene S, Damsky W, van Dijk D, Lee AI, Chun HJ. A neutrophil activation signature predicts critical illness and mortality in COVID-19. Blood Advances 2021, 5: 1164-1177. PMID: 33635335, PMCID: PMC7908851, DOI: 10.1182/bloodadvances.2020003568.Peer-Reviewed Original ResearchConceptsCritical illnessHealth system databaseNeutrophil activationCOVID-19Neutrophil activation signatureSevere COVID-19Intensive care unitGranulocyte colony-stimulating factorHigh mortality rateColony-stimulating factorSystem databaseHepatocyte growth factorClinical decompensationNeutrophil countImmune hyperactivationCare unitEarly elevationLipocalin-2Interleukin-8Longitudinal cohortClinical dataMortality ratePatientsIllnessActivation signature
2020
Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study
Goshua G, Pine AB, Meizlish ML, Chang CH, Zhang H, Bahel P, Baluha A, Bar N, Bona RD, Burns AJ, Dela Cruz CS, Dumont A, Halene S, Hwa J, Koff J, Menninger H, Neparidze N, Price C, Siner JM, Tormey C, Rinder HM, Chun HJ, Lee AI. Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. The Lancet Haematology 2020, 7: e575-e582. PMID: 32619411, PMCID: PMC7326446, DOI: 10.1016/s2352-3026(20)30216-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBetacoronavirusBiomarkersBlood Coagulation DisordersCoronavirus InfectionsCOVID-19Critical IllnessCross-Sectional StudiesEndothelium, VascularFemaleFollow-Up StudiesHumansIntensive Care UnitsMaleMiddle AgedPandemicsPneumonia, ViralPrognosisSARS-CoV-2Vascular DiseasesYoung AdultConceptsCOVID-19-associated coagulopathyNon-ICU patientsIntensive care unitKaplan-Meier analysisSoluble P-selectinCross-sectional studyPlatelet activationHospital dischargeICU patientsSoluble thrombomodulinEndothelial cellsVWF antigenCOVID-19P-selectinSingle-center cross-sectional studyLaboratory-confirmed COVID-19Medical intensive care unitSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesisVon Willebrand factor antigenSoluble thrombomodulin concentrationsVWF antigen concentrationEndothelial cell injurySoluble CD40 ligandMicrovascular complicationsAdult patients
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
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