Featured Publications
Unfolded Protein Response Differentially Modulates the Platelet Phenotype
Jain K, Tyagi T, Du J, Hu X, Patell K, Martin KA, Hwa J. Unfolded Protein Response Differentially Modulates the Platelet Phenotype. Circulation Research 2022, 131: 290-307. PMID: 35862006, PMCID: PMC9357223, DOI: 10.1161/circresaha.121.320530.Peer-Reviewed Original ResearchConceptsUPR pathwayProtein responseMouse plateletsUnfolded protein responseActivation of UPRPlatelet phenotypeTranscriptional regulationGenomic regulationProtein misfoldingAnucleate plateletsProtein aggregationUPR activationPhosphorylation of PLCγ2Chemical chaperonesXBP1 pathwayP38 MAPKPERK pathwayUPRPKCδ activationPlatelet physiologyActivation pathwayPathwayPhenotypeIRE1α inhibitionSelective inductionA guide to molecular and functional investigations of platelets to bridge basic and clinical sciences
Tyagi T, Jain K, Gu S, Qiu M, Gu V, Melchinger H, Rinder H, Martin K, Gardiner E, Lee A, Tang W, Hwa J. A guide to molecular and functional investigations of platelets to bridge basic and clinical sciences. Nature Cardiovascular Research 2022, 1: 223-237. PMID: 37502132, PMCID: PMC10373053, DOI: 10.1038/s44161-022-00021-z.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsVascular smooth muscle cellsPlatelet functional assaysCoronavirus disease 2019Smooth muscle cellsImmune cellsImmune regulationVascular remodelingDisease 2019Pathophysiological processesTranslational relevancePatient diagnosisFlow cytometryMuscle cellsPlatelet biologyFunctional assaysPlatelet investigationsHomeostatic processesPlateletsPhenotypic heterogeneityFunctional stateClinical scienceCellsAdditional roleThrombosisSuch diverse functionsThrombocytopathy and endotheliopathy: crucial contributors to COVID-19 thromboinflammation
Gu SX, Tyagi T, Jain K, Gu VW, Lee SH, Hwa JM, Kwan JM, Krause DS, Lee AI, Halene S, Martin KA, Chun HJ, Hwa J. Thrombocytopathy and endotheliopathy: crucial contributors to COVID-19 thromboinflammation. Nature Reviews Cardiology 2020, 18: 194-209. PMID: 33214651, PMCID: PMC7675396, DOI: 10.1038/s41569-020-00469-1.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAdministration, InhalationAnticoagulantsBlood Coagulation DisordersBlood Platelet DisordersCOVID-19COVID-19 Drug TreatmentEndothelium-Dependent Relaxing FactorsEndothelium, VascularEpoprostenolHeart Disease Risk FactorsHumansIloprostInflammationNitric OxidePlatelet Aggregation InhibitorsSARS-CoV-2Systemic Inflammatory Response SyndromeThrombosisThrombotic MicroangiopathiesVascular DiseasesVasodilator AgentsVenous ThromboembolismConceptsCardiovascular risk factorsRisk factorsCOVID-19Severe acute respiratory syndrome coronavirus 2Pre-existing cardiovascular diseaseAcute respiratory syndrome coronavirus 2Traditional cardiovascular risk factorsAcute respiratory distress syndromeRespiratory syndrome coronavirus 2Respiratory distress syndromeManagement of patientsSyndrome coronavirus 2COVID-19 pathologyCoronavirus disease 2019Potential therapeutic strategyCytokine stormEndothelial dysfunctionThrombotic complicationsDistress syndromeExcessive inflammationCoronavirus 2Severe outcomesAdvanced ageCardiovascular diseaseDisease 2019Age 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 pathologyPatientsPlatelet-derived TLT-1 promotes tumor progression by suppressing CD8+ T cells
Tyagi T, Jain K, Yarovinsky TO, Chiorazzi M, Du J, Castro C, Griffin J, Korde A, Martin KA, Takyar SS, Flavell RA, Patel AA, Hwa J. Platelet-derived TLT-1 promotes tumor progression by suppressing CD8+ T cells. Journal Of Experimental Medicine 2022, 220: e20212218. PMID: 36305874, PMCID: PMC9814191, DOI: 10.1084/jem.20212218.Peer-Reviewed Original ResearchConceptsCD8 T cellsT cellsTLT-1Non-small cell lung cancer patientsCell lung cancer patientsTREM-like transcript-1Tumor immunosuppressive mechanismsT cell suppressionLung cancer patientsPatient T cellsNF-κB pathwayPatient-derived tumorsDistinct activation phenotypesNSCLC patientsImmunosuppressive mechanismsSyngeneic tumorsHumanized miceImmunoregulatory rolePrognostic significanceImmunocompetent miceCancer patientsCell suppressionActivation phenotypeReduced tumorTumor growth
2023
Lipid remodeling in megakaryocyte differentiation and platelet biogenesis
Jain K, Tyagi T, Hwa J. Lipid remodeling in megakaryocyte differentiation and platelet biogenesis. Nature Cardiovascular Research 2023, 2: 803-804. PMID: 37736249, PMCID: PMC10512809, DOI: 10.1038/s44161-023-00324-9.Peer-Reviewed Original ResearchSOD2 in platelets: with age comes responsibility
Jain K, Gu S, Hwa J. SOD2 in platelets: with age comes responsibility. Journal Of Thrombosis And Haemostasis 2023, 21: 1077-1081. PMID: 36716965, DOI: 10.1016/j.jtha.2023.01.016.Peer-Reviewed Original Research
2022
High Altitude Induced Thrombosis: Challenges and Recent Advancements in Pathogenesis and Management
Tyagi T, Jain K. High Altitude Induced Thrombosis: Challenges and Recent Advancements in Pathogenesis and Management. 2022, 85-101. DOI: 10.1007/978-981-19-1008-1_6.ChaptersMolecular pathogenesisAvailable treatment optionsBlood clot formationPulmonary embolismVenous thrombosisTreatment optionsClinical managementRisk factorsAnimal studiesHigh-altitude hypoxic environmentClot formationSerious disorderPathogenesisThrombosisHypoxic environmentVTEDisordersNumber of humanEmbolismA guide to molecular and functional investigations of platelets to bridge basic and clinical sciences
Tyagi, T., Jain, K., Gu, S.X. et al. A guide to molecular and functional investigations of platelets to bridge basic and clinical sciences. Nat Cardiovasc Res 1, 223–237 (2022). https://doi.org/10.1038/s44161-022-00021-zPeer-Reviewed Original Research
2021
Low-dose Aspirin prevents hypertension and cardiac fibrosis when thromboxane A2 is unrestrained
D'Agostino I, Tacconelli S, Bruno A, Contursi A, Mucci L, Hu X, Xie Y, Chakraborty R, Jain K, Sacco A, Zucchelli M, Landolfi R, Dovizio M, Falcone L, Ballerini P, Hwa J, Patrignani P. Low-dose Aspirin prevents hypertension and cardiac fibrosis when thromboxane A2 is unrestrained. Pharmacological Research 2021, 170: 105744. PMID: 34182131, DOI: 10.1016/j.phrs.2021.105744.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsAntifibrotic AgentsAntihypertensive AgentsAspirinBiomarkersBlood PlateletsBlood PressureCardiomyopathiesCase-Control StudiesCells, CulturedDisease Models, AnimalEssential HypertensionFemaleFibrosisHumansMaleMice, Inbred C57BLMice, KnockoutMiddle AgedMyocytes, CardiacMyofibroblastsPlatelet Aggregation InhibitorsReceptors, EpoprostenolReceptors, ThromboxaneThromboxane A2ConceptsProfibrotic gene expressionEnhanced blood pressureBlood pressureCardiac fibrosisPlatelet TXAHypertensive patientsOverload-induced cardiac fibrosisLow-dose aspirin administrationEarly cardiac fibrosisPlatelet-derived thromboxaneLow-dose aspirinEssential hypertensive patientsEssential hypertension patientsHigh-salt dietSalt-sensitive hypertensionCardiac collagen depositionNumber of myofibroblastsSelective inhibitionGene expressionPrevents hypertensionTP overexpressionUrinary TXMAspirin administrationHypertensive miceAspirin treatment
2020
“CO”ping With a Sticky Situation
Jain K, Tyagi T, Hwa J. “CO”ping With a Sticky Situation. Arteriosclerosis Thrombosis And Vascular Biology 2020, 40: 2344-2345. PMID: 32966131, PMCID: PMC7517721, DOI: 10.1161/atvbaha.120.315158.Commentaries, Editorials and Letters
2019
Role of Platelet Mitochondria: Life in a Nucleus-Free Zone
Melchinger H, Jain K, Tyagi T, Hwa J. Role of Platelet Mitochondria: Life in a Nucleus-Free Zone. Frontiers In Cardiovascular Medicine 2019, 6: 153. PMID: 31737646, PMCID: PMC6828734, DOI: 10.3389/fcvm.2019.00153.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsTranscriptional regulationAvian thrombocytesMammalian plateletsMorphological flexibilityAerobic respirationStress responseMitochondriaPlatelet mitochondriaMitochondria damageProtein expressionCritical roleMetabolic substratesPlatelet lifespanKey roleInjury responseCirculating cellsPathophysiological roleNucleusCellsOrganellesRoleRNAStressSurvivalRegulationMitochondrial MsrB2 serves as a switch and transducer for mitophagy
Lee SH, Lee S, Du J, Jain K, Ding M, Kadado AJ, Atteya G, Jaji Z, Tyagi T, Kim W, Herzog RI, Patel A, Ionescu CN, Martin KA, Hwa J. Mitochondrial MsrB2 serves as a switch and transducer for mitophagy. EMBO Molecular Medicine 2019, 11: emmm201910409. PMID: 31282614, PMCID: PMC6685081, DOI: 10.15252/emmm.201910409.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood PlateletsCell LineDiabetes MellitusFemaleHumansMethionine Sulfoxide ReductasesMice, Inbred C57BLMice, KnockoutMicrofilament ProteinsMicrotubule-Associated ProteinsMitochondriaMitochondrial Membrane Transport ProteinsMitochondrial Permeability Transition PoreMitophagyMutationOxidation-ReductionOxidative StressParkinson DiseaseSignal TransductionUbiquitin-Protein LigasesUbiquitinationConceptsReduced mitophagyOxidative stress-induced mitophagyNovel regulatory mechanismStress-induced mitophagyLC3 interactionMitochondrial matrixDamaged mitochondriaMsrB2Reactive oxygen speciesRegulatory mechanismsMethionine oxidationMitophagyMitochondriaPlatelet apoptosisOxygen speciesPlatelet-specific knockoutApoptosisPathophysiological importanceExpressionImportant roleUbiquitinationParkin mutationsParkinSpeciesLC31454-P: Cerebral Glutathione Is Associated with Insulin Resistance in Older Individuals
PACH J, GROSKREUTZ D, LEVENTHAL J, KNIGHT M, JAIN K, HWA J, JIANG L, GRAAF R, HWANG J. 1454-P: Cerebral Glutathione Is Associated with Insulin Resistance in Older Individuals. Diabetes 2019, 68 DOI: 10.2337/db19-1454-p.Peer-Reviewed Original ResearchInsulin resistanceOlder individualsGSH levelsHOMA-IRReactive oxygen speciesOral glucose tolerance testPrefrontal cortexYoung individualsGlucose tolerance testPlasma reactive oxygen speciesPlasma GSH levelsCerebral GSH levelsCerebral glutathioneTolerance testMetabolic dysfunctionMetabolic diseasesNeurocognitive functionUseful markerCognitive deficitsMetabolic changesOxidative stressCr levelsNational InstituteStriatumVisual-spatial memory
2016
Amelioration of ER stress by 4-phenylbutyric acid reduces chronic hypoxia induced cardiac damage and improves hypoxic tolerance through upregulation of HIF-1α
Jain K, Suryakumar G, Ganju L, Singh SB. Amelioration of ER stress by 4-phenylbutyric acid reduces chronic hypoxia induced cardiac damage and improves hypoxic tolerance through upregulation of HIF-1α. Vascular Pharmacology 2016, 83: 36-46. PMID: 27058435, DOI: 10.1016/j.vph.2016.03.004.Peer-Reviewed Original ResearchMeSH KeywordsAltitudeAnimalsApoptosisApoptosis Regulatory ProteinsChronic DiseaseCytoprotectionDisease Models, AnimalEndoplasmic Reticulum StressHypertrophy, Right VentricularHypoxiaHypoxia-Inducible Factor 1, alpha SubunitMaleMolecular ChaperonesMyocardiumOxidative StressPhenylbutyratesProtein CarbonylationProteolysisRats, Sprague-DawleySignal TransductionTime FactorsUnfolded Protein ResponseUp-RegulationConceptsChronic hypoxiaHIF-1αCardiac damageUnfolded protein responseER stressHypoxic toleranceRight ventricular enlargementExposure of ratsHypoxia-inducible factor-1ER stress modulationEndoplasmic reticulum stressInducible factor-1Ventricular enlargementCardiac injuryCardioprotective actionCardiovascular diseaseCardiac hypertrophyMarked upregulationActivation of UPRUnderlying causeUPR markersHypoxiaReticulum stressConcomitant suppressionFactor 1Enhanced hypoxic tolerance by Seabuckthorn is due to upregulation of HIF-1α and attenuation of ER stress
Jain K, Suryakumar G, Prasad R, Ganju L, Singh S. Enhanced hypoxic tolerance by Seabuckthorn is due to upregulation of HIF-1α and attenuation of ER stress. Journal Of Applied Biomedicine 2016, 14: 71-83. DOI: 10.1016/j.jab.2015.10.001.Peer-Reviewed Original ResearchHIF-1αHypoxic toleranceER stressAnti-inflammatory effectsPro-survival effectsFree radical productionCardioprotective actionCardiac damageHO-1NF-κBHerbal supplementsKey adaptive responseOxidative stressTwo-fold increaseHsp70 levelsAntioxidant potentialProtein carbonylationRadical productionHypoxiaSignificant declineSignaling cascadesAdaptive responseCross talkNovel insightsRedox homeostasis
2014
P436Role of myocardial proteostasis in hypoxic tolerance: effect of chemical chaperones and er stress inducers
Jain K, Ganju L, Suryakumar G. P436Role of myocardial proteostasis in hypoxic tolerance: effect of chemical chaperones and er stress inducers. Cardiovascular Research 2014, 103: s80-s80. DOI: 10.1093/cvr/cvu091.115.Peer-Reviewed Original ResearchChemical chaperonesProtein modificationER stressStress inducersHypoxic toleranceRole of proteinsOxidative protein modificationsER stress inducersHeat shock protein expressionStress toleranceProtein homeostasisInhibition of apoptosisProtein misfoldingShock protein expressionEnvironmental stressHarsh environmental conditionsExpression analysisER stress activationChaperonesUPR markersGreater protein oxidationER stress markersBiochemical assaysEnvironmental conditionsProtein oxidation
2013
Myocardial ER chaperone activation and protein degradation occurs due to synergistic, not individual, cold and hypoxic stress
Jain K, Suryakumar G, Prasad R, Singh SN, Ganju L. Myocardial ER chaperone activation and protein degradation occurs due to synergistic, not individual, cold and hypoxic stress. Biochimie 2013, 95: 1897-1908. PMID: 23816873, DOI: 10.1016/j.biochi.2013.06.018.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCold TemperatureEndoplasmic Reticulum StressGene Expression RegulationHeat-Shock ProteinsHypoxiaHypoxia-Inducible Factor 1, alpha SubunitLipid PeroxidationMaleMyocardiumOxidation-ReductionProteasome Endopeptidase ComplexProtein CarbonylationProtein Disulfide-IsomerasesProtein FoldingProteolysisRatsRats, Sprague-DawleyTranscription Factor CHOPTunicamycinConceptsStress responseHypoxic stressCellular stress responseCell survival kinasesProtein oxidationEndoplasmic reticulum stress responseER stress responseER stress inducersReticulum stress responseMyocardial protein oxidationER chaperone GRP78Chaperone activationMisfolded proteinsEnvironmental stressProtein degradationChaperone GRP78Cold stressSurvival kinasesProtein oxidative modificationStress inducersHigh altitude stressMolecular levelCHOP expressionMatrix remodelingProteinUpregulation of Cytoprotective Defense Mechanisms and Hypoxia-Responsive Proteins Imparts Tolerance to Acute Hypobaric Hypoxia
Jain K, Suryakumar G, Prasad R, Ganju L. Upregulation of Cytoprotective Defense Mechanisms and Hypoxia-Responsive Proteins Imparts Tolerance to Acute Hypobaric Hypoxia. High Altitude Medicine & Biology 2013, 14: 65-77. PMID: 23537263, DOI: 10.1089/ham.2012.1064.Peer-Reviewed Original ResearchMeSH KeywordsAltitudeAnimalsAtmospheric PressureCatalaseCreatine Kinase, MB FormDyspneaEndothelin-1ErythropoietinHeme Oxygenase-1HSP70 Heat-Shock ProteinsHSP90 Heat-Shock ProteinsHypoxiaHypoxia-Inducible Factor 1, alpha SubunitMaleMalondialdehydeMyocarditisMyocardiumNitric OxideOxidative StressProtein CarbonylationRatsRats, Sprague-DawleyReactive Oxygen SpeciesSuperoxide DismutaseTime FactorsUp-RegulationVascular Endothelial Growth Factor AConceptsEnvironmental stressHypoxia-responsive proteinsSubsequent oxidative damageReactive oxygen species levelsCellular machineryHypoxia-responsive moleculesResponsive genesOxygen species levelsSpecies levelDifferential expressionTolerant animalsDefense mechanismsOxidative damageCytoprotective chaperoneAntioxidant enzymesHypobaric hypoxiaHigh expressionHIF-1αProteinAdult Sprague-Dawley ratsExpressionMyocardial antioxidant enzymesAcute hypobaric hypoxiaSprague-Dawley ratsCK-MB activity