UCLIntilammationdistortstherelationshipbetweenbloodcholesterolandCVmoralityOverall inflamed40-sCRP>10mg/LNon-InflamedIL-6>3.09pg/ml(eedoo e)3020100-140200240120160180220Cholesterol (mg/dl)Liuet al, JAMA 2004;291:451-459
Inflammation distorts the relationship between blood cholesterol and CVmorality Liuetal,JAMA 2004;291:451-459 20 10 0 30 40 120 140 160 180 200 220 240 Cholesterol(mg/dl) Cardiovascularmortality rate (per 100patients) Overall Non-Inflamed inflamed CRP>10mg/L IL-6>3.09pg/ml
UCLQuestion 1whether is inflammation a cause of thereverseepidemiology?Aim:examine the consequences of activation of theinflammatory response inan establishedanimal model of lipid-induced arterialdisease
Question 1 whether is inflammation a cause of the ‘reverse epidemiology’ ? Aim: examine the conseq uences of activation of the inflammatory r esp onse in an established animal model of lipid-induced arterial disease
UCLCirculationPeripheralcellLiverLDL-CHLDLrLDL-CHVLDLHMGCOARHDL-CHSR-BHDL-CHFXRCholesterol effluxABCA1 bieGeneapoA1 Pre-B-HDLRuan, X.Z.et al.Arterioscler Thromb Vasc Biol2006;26:150-155,Ruan, et al.Kidney Int.56:440-45,199Ruanetal.JAmSocNehrol14:593-600,2003Ruan et al,KidneyInt60:1716-1725,2001)
ABCA1 Gene apoA1 Pre-B-HDL Cholesterolefflux LDLr HDL-CH LDL-CH IL1β LDL-CH HDL-CH SR-B VLDL FXR Peripheral cell Circulation Live r bile HMGCoAR Ruan, X. Z. et al. Arterioscler Thromb Vasc Biol 2006;26:1 50-1 55, Ruan et al. J Am So c Nehrol 14: 593-600, 2003. Ruan, et al. Kidney Int. 56: 440-45, 199 Ruan et al. Kidney Int 60: 1716-1725, 2001)
UCLIn vivo chronic inflammatorymodel:ApoE KO(Diet: 21% fat &-0.15% cholesterol)InflammationgroupControl group(10%Casein,SCinjection(saline,SCinjection5dayperweek,n=75day perweek,n=7)8 weeksplasma cholesterol level/atherosclerosis
Inflammation group (10%Casein, SC injection 5 day per week, n=7) plasma cholesterol level /atherosclerosis Control group (saline, SC injection 5day per week, n=7) 8 we e ks ApoE KO (Diet: 21% fat & 0.15% cholesterol) In vivo chronic inflammatorymodel:
UCLSubcutaneous casein injection associatedlevels:withhigher serum amyloidAand TNF5000060CNTLCNTL8888Caseincasein5040000中40P<0.01P<0.01/Bu)30000BalNs20000100001000
Serum TNF concentration (ng/ml) 0 10000 20000 30000 40000 50000 CNTL Casein * SAA level (ng/ml) 0 10 20 30 40 50 60 CNTL casein * Subcutaneous casein injection associated with higher serum amyloid A and TNF levels: P<0.01 P<0.01