Physicians' Academy for Cardiovascular Education

Prof Kathryn Tan

Slides (presentation) - Jan. 20, 2010

The Vascular Wall and Diabetes
Relativerisksforfatalcoronaryheartdiseaseinmenandwomenwithandwithoutdiabetes(meta-analysisof22prospectivecohortstudies
Diabetes – A Vascular Disease
PutativeMechanismsforAcceleratedAtherosclerosisinType2Diabetes
Transverse section of LAD from a 72 year old type 2 DM
Non-enzymatic Glycation
FormationofAdvancedGlycationEndProducts
Formation of AGEs
Advanced Glycation End Products
IncreasedserumAGEspredictscardiovascularmortalityintype2DM
AGELevelsinSkinCollagenPredicttheRiskofFuture10-YearProgressionofDiabeticNephropathyintheDCCT/EDICStudy
Advanced Glycation End Products and Atherosclerosis
Non-receptor-mediated effects of AGEs on atherogenesis
Decrease vascular compliance in type 2 diabetes
AGEs and Decreased Vascular Compliance in Diabetes
AGEcross-linkbreakersreducelargearterystiffness
Formation of AGEs on plasma lipoproteins
FormationofAGEsinglycoxidizedLDLinvitro
IncreasedapoB-CMLintype2DM
Biological Effects of AGE-modified LDL
AGEs Potentiate the Atherogenic Effects of Dyslipidaemia in Diabetes
Advanced Glycation End Products and Atherosclerosis
Structure of full-length RAGE and its splice variants
Endothelialdysfunctionintype2diabetes
AGEandImpairedEndothelium-dependentVasodilationinDiabetes
AGEsReducesNOProductionbyDown-regulationofEndothelialNitricOxideSynthase
EffectofAGE-BSAoneNOSBlockedbyAnti-RAGEAntibody
Dia 28
Therapeutic options
Advanced Glycation End Product Interventions Reduce Diabetes-Accelerated Atherosclerosis
Atheroscleroticplaqueareaattenuatedby30%withALT-711andby40%inAG-treatedmice
BlockadeofAGE-RAGEaxiswithsRAGEsuppressesprogressionofestablishedatherosclerosisinapoE-nullmice
PharmacologicalModulationofsRAGE
Type2DMrandomisedtoreceiveadd-ontherapywithrosiglitazoneorsulphonylurea
Type 2 DM randomised to atorvastatin or placebo
Pharmacological modulation of soluble RAGE
Endothelialdysfunctionandvascularinflammation
Acknowledgement

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