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
CELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation
Esteghamat F, Broughton JS, Smith E, Cardone R, Tyagi T, Guerra M, Szabó A, Ugwu N, Mani MV, Azari B, Kayingo G, Chung S, Fathzadeh M, Weiss E, Bender J, Mane S, Lifton RP, Adeniran A, Nathanson MH, Gorelick FS, Hwa J, Sahin-Tóth M, Belfort-DeAguiar R, Kibbey RG, Mani A. CELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation. Nature Genetics 2019, 51: 1233-1243. PMID: 31358993, PMCID: PMC6675645, DOI: 10.1038/s41588-019-0470-3.Peer-Reviewed Original ResearchConceptsEarly-onset atherosclerosisMetabolic syndromeMetabolic syndrome traitsWhole-exome sequence analysisAttractive therapeutic targetPlatelet hyperactivationInsulin levelsPlasma insulinPlasma levelsInsulin sensitivityInsulin secretionTherapeutic targetPlatelet activationDisease mechanismsSyndrome traitsAtherosclerosisFunction mutationsSyndromeNovel lossInsulinMutationsSecretionAge associated non-linear regulation of redox homeostasis in the anucleate platelet: Implications for CVD risk patients
Jain K, Tyagi T, Patell K, Xie Y, Kadado AJ, Lee SH, Yarovinsky T, Du J, Hwang J, Martin KA, Testani J, Ionescu CN, Hwa J. Age associated non-linear regulation of redox homeostasis in the anucleate platelet: Implications for CVD risk patients. EBioMedicine 2019, 44: 28-40. PMID: 31130473, PMCID: PMC6604369, DOI: 10.1016/j.ebiom.2019.05.022.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAge FactorsAgedAged, 80 and overAgingAnimalsAntioxidantsApoptosisBiomarkersBlood PlateletsCardiovascular DiseasesComorbidityDisease Models, AnimalFemaleHomeostasisHumansMaleMiceMiddle AgedOxidation-ReductionOxidative StressPlatelet ActivationPlatelet AdhesivenessReactive Oxygen SpeciesRisk AssessmentRisk FactorsConceptsRisk patientsMouse studiesPlatelet phenotypeMajor adverse cardiovascular eventsHigh cardiovascular risk patientsAdaptive increaseAdverse cardiovascular eventsCentral pathophysiological roleCVD risk patientsCardiovascular risk patientsAggressive antiplatelet therapyEffect of comorbidityAge group 40Young healthy subjectsAntiplatelet therapyCardiovascular eventsYear age cohortAdvanced ageCVD patientsGroup 40Healthy subjectsPathophysiological roleElderly populationCardiovascular pathologyPatients
2014
Aldose Reductase–Mediated Phosphorylation of p53 Leads to Mitochondrial Dysfunction and Damage in Diabetic Platelets
Tang WH, Stitham J, Jin Y, Liu R, Lee SH, Du J, Atteya G, Gleim S, Spollett G, Martin K, Hwa J. Aldose Reductase–Mediated Phosphorylation of p53 Leads to Mitochondrial Dysfunction and Damage in Diabetic Platelets. Circulation 2014, 129: 1598-1609. PMID: 24474649, PMCID: PMC3989377, DOI: 10.1161/circulationaha.113.005224.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAldehyde ReductaseAnimalsApoptosisBcl-X ProteinBlood PlateletsCarotid Artery DiseasesDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2Disease Models, AnimalFemaleHumansMaleMiceMice, Inbred C57BLMice, KnockoutMiddle AgedMitochondrial DiseasesPhosphorylationSignal TransductionThrombosisTumor Suppressor Protein p53ConceptsMitochondrial dysfunctionHyperglycemia-induced mitochondrial dysfunctionP53 phosphorylationAntiapoptotic protein Bcl-xL.Platelet apoptosisMitochondrial damageMitochondrial membrane potentialReductase activationActivation of p53Reactive oxygen species productionOxygen species productionBcl-xL.Molecular pathwaysSevere mitochondrial damagePhosphorylationNovel therapeutic targetAldose reductase activationSpecies productionMembrane potentialApoptosisCentral roleTherapeutic targetDose-dependent mannerActivationP53