Anthocyanin-Rich Purple Corn Extract Inhibit Diabetes-Associated Glomerular Angiogenesis.docVIP

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Anthocyanin-Rich Purple Corn Extract Inhibit Diabetes-Associated Glomerular Angiogenesis.doc

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Anthocyanin-Rich Purple Corn Extract Inhibit Diabetes-Associated Glomerular Angiogenesis

Anthocyanin-RichPurpleCornExtractInhibitDiabetes- AssociatedGlomerularAngiogenesis Min-KyungKang1,SoonSungLim1,Jae-YongLee2,KyungMokYeo3,Young-HeeKang1* 1Department of Food and Nutrition and Center for Aging and Healthcare, Hallym University, Chuncheon, Korea, 2Department of Biochemistry, School of Medicine, HallymUniversity,Chuncheon,Korea,3SDCo.,Ltd,Chuncheon,Korea Abstract Diabeticnephropathy (DN)isoneofthemajordiabeticcomplications andtheleadingcauseofend-stagerenaldisease. AbnormalangiogenesisresultsinnewvesselsthatareoftenimmatureandplayapathologicalroleinDN,contributingto renalfibrosisanddisruptingglomerularfailure.Purplecornhasbeenutilizedasadailyfoodandexertsdisease-preventive activities.Thisstudywasdesignedtoinvestigatewhetheranthocyanin-richpurplecornextract(PCE)preventedglomerular angiogenesisunderhyperglycemicconditions.Humanendothelialcellswereculturedinconditionedmediaofmesangial cellsexposedto33mMhighglucose(HG-HRMC-CM).PCEdecreasedendothelialexpressionofvascularendothelialgrowth factor(VEGF)andhypoxiainduciblefactor(HIF)-1ainducedbyHG-HRMC-CM.Additionally,PCEattenuatedtheinductionof theendothelialmarkerofplateletendothelialcelladhesionmolecule(PECAM)-1andintegrinb3enhancedinHG-HRMC-CM. Endothelial tube formation promoted by HG-HRMC-CM was disrupted in the presence of PCE. In the invivo study employingdb/dbmicetreatedwith10mg/kgPCEfor8weeks,PCEalleviatedglomerularangiogenesisofdiabetickidneys byattenuatingtheinductionofVEGFandHIF-1a.OraladministrationofPCEretardedtheendothelialproliferationindb/db mouse kidneys, evidenced by its inhibition of the induction of vascular endothelium-cadherin, PECAM-1 and Ki-67. PCE diminishedthemesangialandendothelialinductionofangiopoietin(Angpt)proteinsunderhypeglycemicconditions.The induction and activation of VEGF receptor 2 (VEGFR2) were dampened by treating PCE to db/db mice. These results demonstratethatPCEantagonizedglomerularangiogenesisduetochronichyperglycemiaanddiabetesthroughdisturbing the Angpt-Tie-2