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 lossInsulinMutationsSecretion
2015
Hyperglycemia repression of miR-24 coordinately upregulates endothelial cell expression and secretion of von Willebrand factor
Xiang Y, Cheng J, Wang D, Hu X, Xie Y, Stitham J, Atteya G, Du J, Tang WH, Lee SH, Leslie K, Spollett G, Liu Z, Herzog E, Herzog RI, Lu J, Martin KA, Hwa J. Hyperglycemia repression of miR-24 coordinately upregulates endothelial cell expression and secretion of von Willebrand factor. Blood 2015, 125: 3377-3387. PMID: 25814526, PMCID: PMC4447857, DOI: 10.1182/blood-2015-01-620278.Peer-Reviewed Original ResearchConceptsVon Willebrand factorDiabetes mellitusMiR-24Diabetic patientsAdverse thrombotic eventsThrombotic cardiovascular eventsVWF expressionWillebrand factorDiabetic mouse modelNovel therapeutic targetHistamine H1 receptorsEndothelial cell expressionHyperglycemia-induced activationCardiovascular eventsThrombotic eventsH1 receptorsMouse modelVWF levelsTherapeutic targetCell expressionMellitusPatientsEndothelial cellsElevated levelsReactive oxygen species
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