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Presentation1
1. Heart dialysis systemHeart dialysis system
Studying the effect of systemic apoA-1 treatmentStudying the effect of systemic apoA-1 treatment
on carotid atherosclerotic plaqueon carotid atherosclerotic plaque
Studying the effect of LDL aphaeresis on LDL,Studying the effect of LDL aphaeresis on LDL,
plasma inflammatory markers, and cytokinesplasma inflammatory markers, and cytokines
comparing the effect of local high dose of apoA1comparing the effect of local high dose of apoA1
on atherosclerotic plaque versus systemic therapyon atherosclerotic plaque versus systemic therapy
Comparing the effect of single therapy versusComparing the effect of single therapy versus
multiple therapymultiple therapy
2. Animal studyAnimal study
25 Rabbits25 Rabbits
Cholesterol fed diet (1%)Cholesterol fed diet (1%)
Inducing vascular injury in carotid arteriesInducing vascular injury in carotid arteries
Systemic LDL aphaeresisSystemic LDL aphaeresis
Systemic apoA-1 administrationSystemic apoA-1 administration
Local apoA-1 administrationLocal apoA-1 administration
Studying the effect of apoA-1 on plaque asStudying the effect of apoA-1 on plaque as
well as lipid profilewell as lipid profile
Studying the effect of LDL aphaeresis onStudying the effect of LDL aphaeresis on
lipid profilelipid profile
3. Heart Dialysis System In RabbitsHeart Dialysis System In Rabbits
25 (wattanabe) rabbits
1%Cholesterol fed diet
Control group:
No treatment
N#10
Systemic treatment:
LDL aphaeresis
Systemic apoA1
Local treatment:
of apoA1
Systemic LDL aphaeresis
Single session therapy
N#5
Sacrified after 48 h
N#5
Sacrified after 6th
w
Weekly for 5 w
Sacrified at 6th
w
Sacrified at 6th
w
N#10N#5
5. Measured indicesMeasured indices
Biochemical measurementsBiochemical measurements
Lipid profileLipid profile
LDL, HDL, and TGLDL, HDL, and TG
CRPCRP
Lp(a)Lp(a)
FibrinogenFibrinogen
PlasminogenPlasminogen
Anti-thrombinAnti-thrombin
C3, C4, C1 inhibitorC3, C4, C1 inhibitor
Interlukin-1Interlukin-1
TNF alphaTNF alpha
EdotoxinsEdotoxins
FerritinFerritin
CD 14CD 14
Tissue factorTissue factor
Before, 1 h, 6h, 24h after treatmentBefore, 1 h, 6h, 24h after treatment
Histological studyHistological study
Intimal thichnessIntimal thichness
Intima/medail ratioIntima/medail ratio
Lipid content of the plaqueLipid content of the plaque
Macrophage content of theMacrophage content of the
plaqueplaque
Smooth muscle cell of polaqueSmooth muscle cell of polaque
6. Local infusion of ApoA-1m in toLocal infusion of ApoA-1m in to
carotid artery of rabbitcarotid artery of rabbit
25 rabbits25 rabbits
1.5% cholesterol diet for 90 days1.5% cholesterol diet for 90 days
Perivascular electrical injuryPerivascular electrical injury
G1:salineG1:saline
G2:phospholipid vesicleG2:phospholipid vesicle
G3,4,5:Apo A-1m :250-500-1000 mgG3,4,5:Apo A-1m :250-500-1000 mg
Local delivery through IVUS catheterLocal delivery through IVUS catheter
Ninety minutes infusionNinety minutes infusion
Giulia ChiesaGiulia Chiesa
8. Study protocolStudy protocol
IVUS study 0, 30m, 60m, 90mIVUS study 0, 30m, 60m, 90m
Blood sample 0, 45,90m , 6,24,48,72hBlood sample 0, 45,90m , 6,24,48,72h
Histologic examination on both carotidsHistologic examination on both carotids
Giulia ChiesaGiulia Chiesa
9. Plasma HDL 72 h after infusionPlasma HDL 72 h after infusion
Giulia ChiesaGiulia Chiesa
11. Inhibition of carotid intimal thickening by apoA-1mInhibition of carotid intimal thickening by apoA-1m
in rabbitsin rabbits
New Zealand white rabbitsNew Zealand white rabbits
1% cholesterol-fed1% cholesterol-fed
Flexible collar application at 21Flexible collar application at 21stst
dayday
of dietof diet
EPC+A-1m(119+40mg)EPC+A-1m(119+40mg)
EPC(119mg)EPC(119mg)
Maurizio and SomaMaurizio and Soma
12. Study protocolStudy protocol
Maurizio andMaurizio and
SomaSoma
NZWR
1% cholesterol diet
EPC+A-!m EPC control
Significant
intimal
thickening
Drug before injury
Sig decrease in intima
Drug the day of injury
No sig change
No decrease in intima
13. Effect of various regimensEffect of various regimens
Maurizio and SomaMaurizio and Soma
I/M ratio
Control
0.63+/-o.11
EPC treated
0.50+/-0.14
A-1m treated
0.26+/-0.19
14. Reduction of intima thickening inReduction of intima thickening in
hypercholesterolemic rabbithypercholesterolemic rabbit
1% Cholesterol fed rabbits1% Cholesterol fed rabbits
Balloon injured ileofemoral arteriesBalloon injured ileofemoral arteries
G1: apoA-1m+phospholipidG1: apoA-1m+phospholipid
G2: phospholipidG2: phospholipid
G3: controlG3: control
PK Shah et allPK Shah et all
15. Intimal thicknessIntimal thickness
PK Shah et allPK Shah et all
Control
1.69+/-0.43
mm2
Carrier treated
1.14+/-0.38
mm2
A-1m treated
o.49+/-0.29
mm2
16. Intima-Media RatioIntima-Media Ratio
Control:2.1+/-0.1Control:2.1+/-0.1
Carrier :1.5+/-0.5Carrier :1.5+/-0.5
Apo1-A:0.7+/-0.2Apo1-A:0.7+/-0.2
PK Shah et allPK Shah et all
17. Intimal lesion covered by macrophagesIntimal lesion covered by macrophages
Carrier treated:59.3+/-12.3%Carrier treated:59.3+/-12.3%
ApoA-1 treated:25.3+/-17%ApoA-1 treated:25.3+/-17%
PK Shah et allPK Shah et all
18. conclusionconclusion
Apo A-1m significantlyApo A-1m significantly
Reduces intimal thickeningReduces intimal thickening
Reduces macrophage contentReduces macrophage content
PK Shah et allPK Shah et all
19. ApoA-1m in EKO miceApoA-1m in EKO mice
EKO mice fed with high cholesterolEKO mice fed with high cholesterol
G1:Control(saline treated)G1:Control(saline treated)
G2:Carrier (Phosphatidylcholine)G2:Carrier (Phosphatidylcholine)
G3:Apoa-1 treated+phospholipidG3:Apoa-1 treated+phospholipid
PK ShahPK Shah
20. ResultsResults
1.6-fold increase in tissue cholesterol1.6-fold increase in tissue cholesterol
mobilization in apoA-1 groupmobilization in apoA-1 group
40%-50% decrease in plaque lipid40%-50% decrease in plaque lipid
content in apoA-1 groupcontent in apoA-1 group
29%-36% decease in macrophage29%-36% decease in macrophage
content in apoA-1 groupcontent in apoA-1 group
PK Shah et allPK Shah et all