《儿科学》课程教学课件（PPT讲稿）27 Inflammation Causes Cholesterol Redistribution by Diverting Cholesterol from Circulation to Tissue Tompartments

UCLInflammation causes cholesterol redistributionbydiverting cholesterol from circulation to tissuecompartments

Inflammation causes cholesterol redistribution by diverting cholesterol from circulation to tissue compartments

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2000 0 4000 6000 NHS University Highly Cited Publications Good strength in Basic Science Highest performing UK University in Biomedicine (RAE) International Leaders in Neuroscience Research. Growing Research Award Portfolio Investment in infrastructure, people and partnerships Strong and established R&D platform for UCLPartners R&D: UCL European Leaders in Research in Clinical Medicine 22 Nobel Prize. 4th ranked in the world

UCLChronic Renal DiseaseDiabetesOther inflammatory diseaseMOORHEAD(Cause)HypothesisMoorhead et al LancetVLDL↑ ↑1982VLDL remnants ↑Small dense LDL ↑Ruan etalHDLNature ReviewNephrology,2009InflammationAtherosclerosis/NAFL

VLDL VLDL remnants Small dense LDL HDL Chronic Renal Disease Diabetes Other inflammatory disease Atherosclerosis/NAFL (Cause) Inflammation MOORHEAD Hyp othesis Moorhead et al Lancet 1982 Ruan et al Nature Review Nephrology, 2009

UCLMesangial foam cellsGlomerular capillariesa siteforatherosclerosis*AB

Mesangial foam cells Glomerularcapillariesa siteforatherosclerosis* A B C

UCLAnnual mortality rates from CV disease0.28%General population32X33X2X9.12%Haemodialysis9.24%Peritoneal dialysisTransplant recipients 0. 54%Levey et alAJKD 1998;32:853-906

Annual mortality rates from CVdisease 0.28% 9.12% 9.24% • Generalpopulation • Haemodialysis • Peritonealdialysis • Transplant recipients0.54% LeveyetalAJKD 1998;32:853-906 32X 33X 2X

UCLCardiovascular mortality in dialysis patientswithrenaldysfunction100Levey et alAJKD 1998:32:853(%) en10+ Dialysis MaleDialysis Femald0.1+ Control Male--Control Female0.01 Transplant pts器25-34 35-44 45-54 55-64 65-74 75-84>85Age (years)

Cardiovascular mortality in dialysis patients with renal dysfunction Age (years) Annual Mortality (%) 0.01 0.1 10 1 100 25-34 35-44 45-54 55-64 65-74 75-84 >85 Dialysis Male Dialysis Female Control Male Control Female LeveyetalAJKD 1998;32:853 Transplant pts

UCLChronic Renal DiseaseNephrotic syndromeChronic renal failureRenal transplantation(Consequence)+VLDLVLDL remnants(prim ary)Small dense LDLHDL*accumulationof lipid&cell debrisInflammatory cell infiltratimAtherosclerosisSMC proliferation

VLDL VLDL remnants Small dense LDL HDL Atherosclerosis Chronic Renal Disease Nephrotic syndrome Chronic renal failure Renal transplantation (Consequence) (prim ary) accumulationoflipid&celldebris Inflammatory cell infiltration SMC proliferation

UCLTotal Cholesterol and Cardiovascular Mortalityamong 350,000 men: MRFITProspective Study2.0ee1.00.5-6. 07.04.05.0Usual total cholesterol (mmol/1)Martin et al, Lancet1986;2(8513) :933-936

Total Cholesterol and Cardiovascular Mortality among 350,000 men: MRFIT Prospective Study 2.0 1.0 0.5 4.0 RelativeriskofCHD death 5.0 6.0 7.0 Usual total cholesterol (mmol/l) Martin et al, Lancet1986;2(8513):933-936

UCLTotal Cholesterol and Cardiovascular Mortalityin dialysis patients40ee Overall(Sedo e)3020-10-0-240120140160180200220Cholesterol (mg/dl)Liuet al, JAMA 2004;291:451-459

Liuetal,JAMA 2004;291:451-459 120 140 160 180 200 220 240 Cholesterol(mg/dl) Cardiovascularmortality rate (per 100patients) Total Cholesterol and Cardiovascular Mortality in dialysis patients 40 Overall 30 20 10 0