遗传性极度高甘油三酯小鼠模型

烦恼有何惧怕，既然躲不掉，就调好心态与它共存。心向阳光，何惧风霜。

茫茫人海你我相遇就是缘分，欢迎下载！2021/4/262Distinctphenotypesinseverehypertriglyceridemicmice:

spontaneousatherosclerosis,pancrearitis,impairedhemorheologyandabnormalneuronaldevelopment

2021/4/263HyperTGintheworld:

Meta,multi-variables,Epidemiologicalanalysis:HyperTGisanindependentriskfactorofcoronaryarterydisease2021/4/264S447X,anaturallyoccurringC-terminaltwoaminoacidtruncationmutation wildtypeLPL----------------------KKSG S447XLPL----------------------KK

Incidence:18.8%ofCaucasian,25.4%Chinese,and3%ofAustralianAborigineassociatedwith:

LowTG,HighHDL-C,LowCHDCompleteRescueofLipoproteinLipase-DeficientMicebySomaticGeneTransferoftheNaturallyOccurringLPLS447XBeneficialMutation.

Arterioscl.Thromb.Vasc.Biol.2005Jul7

2021/4/265%SurvivalrateofLPL-/-pupsDaysafterBirthTheUniqueHyperTGMouseModels

AdultLPL-/-mice2021/4/266

TC TGWT 58±5.8 79±22.0ApoE0 304±10.2* 145±51.9*LPL0 189±58.0* 3199±773.2*ApoE0/LPL0 817±166.7* 5988±857.4*PlasmaLipidsLevelsofKOMice2021/4/267AAV-MediatedlongtermLPLgenetherapyformurineextremeHTG

2021/4/2682021/4/269LK-/->15mWT>15mLesion

Quantitation2021/4/2610LK-/-10mWT10mLK+/-10m

3outof8,37％2021/4/2611WTLK+/-LK-/-4m>15m10mPending9、人的价值，在招收诱惑的一瞬间被决定。2023/2/32023/2/3Friday,February3,202310、低头要有勇气，抬头要有低气。2023/2/32023/2/32023/2/32/3/20234:56:34PM11、人总是珍惜为得到。2023/2/32023/2/32023/2/3Feb-2303-Feb-2312、人乱于心，不宽余请。2023/2/32023/2/32023/2/3Friday,February3,202313、生气是拿别人做错的事来惩罚自己。2023/2/32023/2/32023/2/32023/2/32/3/202314、抱最大的希望，作最大的努力。03二月20232023/2/32023/2/32023/2/315、一个人炫耀什么，说明他内心缺少什么。。二月232023/2/32023/2/32023/2/32/3/202316、业余生活要有意义，不要越轨。2023/2/32023/2/303February202317、一个人即使已登上顶峰，也仍要自强不息。2023/2/32023/2/32023/2/32023/2/32021/4/2613LK-/-4mWT4mLK+/-4m

（40×）2021/4/2614MacrophageWT10MOilredOLK+/-15m

LK-/-15m（200×）2021/4/2615VCAM-1VCAM-1OilredO（200×）LK+/-15m

LK-/-15m2021/4/26164month10month>15monthWT+/--/-WTWT-/--/-2021/4/2617CMoxidation2021/4/261815m10m4mOxidationofchylomicronbyESRanalysis2021/4/2619ROproductionasreflectedbypeakHeightofESRgraph4m10m15m01234564m10m15mProductofRO.(cm/mg)2021/4/2620Spontaneousatherosclerosisinhypertriglyceridemicmurinemodelonnormalchowdiet2021/4/2621AlterationsofBloodCoagulation2021/4/2622

HemorheologicalchangesinthemiceHematocritRBCElectroph.Rate%ofRBCVol.wtE0**50.037.525.012.50L0E0/L01.000.750.500.250Electrophoresisrate2021/4/2623AlterationsofRBCRheology2021/4/2624

AlterationsinRBCpolarizationandmicroviscosityPolarizationMicroviscosityPvalueofRBCghost

wtE0**0.200.150.100.050L0E0/L01.000.750.500.250ηvalueofRBCghost****2021/4/2625

StructuralchangesinRBCmembraneasstudiedbyFTIR:2.Secondarystructureofmembraneproteinß-turnsα-helix

ß-sheetα-helixA=1684A=1659A=1634A=1545AbsorptionvaluewtE0**2.001.501.000.500L0E0/L0***********2021/4/2626Hemorrheologicabnormalitiesinmicewithseverehypertriglyceridemiaandcombinedhypertriglyceridemia/cholesterolemia2021/4/2627Impactofextremehypertriglyceridemiaonatherogenesis:utilizationofApoE/LPLdoubledeficientmice

Aorticlesiondevelopmentat3,6and9monthcomparedwithApoE0andE0/LPL+/-mice;LocalexpressionofactiveandinactivehLPLincarotidarteries:identificationoflipiddeposition;BMTastoolforevaluationofmacrophage-specificdeletionofLPLgene;AsmodelbyFeClinjuryoncarotidarteryforevaluationoftheLPL’seffectonatherogenesis2021/4/2628ApoE-/-XLPL-/-ApoE-/-6months3months2021/4/2629ELK-/-EK-/-ELK+/-（40×）3M6M9MPendingPendingPendingPendingPendingPending2021/4/2630ExternalcarotidarteryCommoncarotidarteryInternalcarotidarteryArterialwallgenetransfertomousecarotidartery2021/4/2631 LocalexpressionofactiveandinactivehLPLincarotidarteriesinWTmice:RealTimequantitationofmRNA1000bp500bp(-)APWT194PM123456β-actin(500bp)400bpLPL(396bp)APLPL-WT LPL194RatioofLPL/actin(X103)122021/4/2632Ctl.LPLstainingLPLGT.LPLStainingCtl.OROstainingLPLGT.OROstainingArterialexpressionofLPLgeneinWTmice:PromotionofLipidDeposition2021/4/2633OROstaininghAPhLPLWThLPL194(200x)(400x)ApoE-/-2021/4/2634OROstaining(200x)(400x)

hAPhLPLWThLPL194LPL-/-2021/4/2635Ad-APAd-LPLwtAd-LPL194enfaceconfocalmicroscopyimagesofVCAM-1expressionLPL-/-2021/4/2636Rapidlipiddepositioninendothelial-intactcarotidarteryviaarterialexpressionofeitheractiveorinactivelipoproteinlipaseinApoEandLPLdeficientmousemodels.2021/4/2637CommoncarotidarteriesofapoE-/-,LPL+/-(ELK)mice(A)andapoE-/-,LPL+/+(EK)mice(B)8weeksafterferricchlorideinjury2021/4/2638neointimaformationaftercarotidarteryinjurybyFeCl3for

8weeksELKcarotidartery,H&EstainingEKnoninjuredinjured2021/4/2639MeanAreaofIntimalandMedialCross-sectionsofEKandELKMice8WeeksafterInjuryEKELK***mediaintimal0246810MeanArea(um2X104)2021/4/2640lipiddepositaftercarotidarteryinjurybyFeCl3for

8weeksELKEKcarotidarterycounterstainedwithOROandhaematoxylininjurednoninjured2021/4/2641lipiddepositaftercarotidarteryinjurybyFeCl3for

4weeksELKEKcarotidarterycounterstainedwithOROandhaematoxylinnoninjuredinjured2021/4/2642Mac3staining（8week’ssample）ELKEKVWFactorStaining2021/4/2643****NSPlasmaTGofELKandEKMiceFedHFD0100200300ELKEKTG(mg/dl)0Week4Week82021/4/2644PlasmaTClevelsofELKandEKMiceFedHFD02505007501000ELKEKTCmg/dl0Week4Week82021/4/2645

AcceleratedatherogenesisinLPLdeficientmiceasassessedbyFeCl3arterialinjuryinApoEknockoutbackground

2021/4/2646PancreatitisinminkswithLPLdeficiency

A.HEstainofpancreasofnormal(topleft)andaffectarea;B.HEstainofsectionfullwithmacrophages;C.SudanIVstainindicatinglipidaccumulation.(Mag.X425)

Christophersenetal,JLR.38:837,19972021/4/2647normalinfiltrationhemorrhagenecrosisSpontaneouspancreatitisinLPL-/-mice（HEX200）2021/4/2648WT4monthLK4month（SirusRedX200）SpontaneouspancreatitisinLPL-/-mice2021/4/2649CtlMouse,C57B6L-arginine(ipat2mg/gBW),72hL-arginine(ipat4mg/gBW),24hL-arginine(ipat3mg/gBW),72hPathologyinL-ArginducedAcutePancreatitis2021/4/2650Changesofserumamylasen=4**2021/4/2651IncreasedsusceptibilitytopancreatitisLPLgenotype

+-+-L-ArgInduction--++**2021/4/2652

NeurologicaldefectsinLPLdeficientmi