ΠΑΝΕΠΙΣΤΗΜΙΟ ΙΩΑΝΝΙΝΩΝ

ΤΜΗΜΑ ΧΗΜΕΙΑΣ

ΕΡΓΑΣΤΗΡΙΟ ΒΙΟΧΗΜΕΙΑΣ

H αθηπωμαηική πλάκα ηος διαβηηικού αζθενή

Αλέξανδπορ Δ. Τζελέπηρ

Καθηγητής Βιοχημείας-Κλινικής Χημείας

Creager MA, et al. Circulation 2003;108:1527

Hyperglycemia increases flux through the polyol pathway

Brownlee M. Diabetes. 2005; 54:1615

Increased production of AGE precursors

Brownlee M. Diabetes. 2005; 54:1615

Pathways of AGEs formation

Jakus V, et al. Physiol. Res. 53: 131-142, 2004

Jakus V, et al. Physiol. Res. 53: 131-142, 2004

Structures of some most important AGEs

Pentosidine, Argpyrimidine,

Carboxymethyllysine (CML),

Carboxyethyllysine (CEL), Pyrraline,

Glyoxal-lysine dimer (GOLD),

Methylglyoxal-lysine dimer (MOLD), Crosslines

RAGE-dependent perpetuated NF-κB activation

Bierhaus A, et al. J Mol Med (2005) 83: 876–886

Consequences of increased AGE production

Brownlee M. Diabetes. 2005; 54:1615

Consequences of hyperglycemia-induced activation of PKC

Brownlee M. Diabetes. 2005; 54:1615

Hyperglycemia increases flux through the hexosamine pathway

Brownlee M. Diabetes. 2005; 54:1615

Oxidative phosphorylation, superoxide production, and scavenging pathways in

Mitochondria

Madamanchi NR, et al. Circ. Res. 2007;100;460-473

Hyperglycemia and Insulin resistance-induced increased mitochondrial

superoxide production activates atherogenic signaling pathways

Madamanchi NR, et al. Circ. Res. 2007;100;460-473

Possible mechanisms by which glucose and AGEs

can affect atherogenesis in diabetes

Mazzone Th, et al. Lancet 2008; 371: 1800–09

Macrophage biology in type-2 diabetes mellitus and atherosclerosis

Mazzone Th, et al. Lancet 2008; 371: 1800–09

Hyperglycemia and endothelium-derived vasoactive substances

Creager MA, et al. Circulation 2003;108:1527-1532

Brownlee M. Diabetes. 2005; 54:1615

eNOS and PGI2 synthase are two critical antiatherogenic enzymes

Mechanisms of platelet activation associated with diabetes mellitus

Ferroni P, et al. J Thromb Haemost 2004; 2: 1282–91

Effects of altered glycemic control on platelet function

Ferroni P, et al. J Thromb Haemost 2004; 2: 1282–91

Creager MA, et al. Circulation 2003;108:1527-1532

Platelet function and plasma coagulation factors are altered in diabetes,

favoring platelet aggregation and a propensity for thrombosis

Metabolic basis of the atherogenic lipoprotein phenotype

in type 2 diabetes

Chapman MJ. Diabetes Vasc Dis Res 2007;4 (Suppl):S5-S8

Σχημαηιζμός πλούζιων ζε TG ζωμαηιδίων VLDL1

Ρόλος ηης HL ζηο μεηαβολιζμό ηων

apoB-λιποπρωηεϊνών

VLDL1

Metabolic basis of the atherogenic lipoprotein phenotype

in type 2 diabetes

Chapman MJ. Diabetes Vasc Dis Res 2007;4 (Suppl):S5-S8

Lipoprotein changes in type 2 diabetes mellitus

Mazzone Th, et al. Lancet 2008; 371: 1800–09

Formation of Gly-ox-LDL and Gly-ox-HDL

Hyperglycemia and Oxidative stress induce dysfunctional HDL

Kontush A, et al. Pharmacol Rev 58:342–374, 2006

Diabetic dyslipidemia and the vessel wall

Mazzone Th, et al. Lancet 2008; 371: 1800–09

Inflammation in diabetic coronary arteries

Burke AP, et al. Arterioscler Thromb Vasc Biol. 2004;24:1266-1271

Type 2-DM

Type 1-DM

Non-Diabetic

Expression of S100A12/ENRAGE (a RAGE-binding protein) in human

coronary lesions from sudden coronary death victims

Burke AP, et al. Arterioscler Thromb Vasc Biol. 2004;24:1266-1271

Diabetes (A–E)

No Diabetes (F–J)

Combined effect of hyperlipidemia and diabetes on

atherosclerotic plaque components

Burke AP, et al. Arterioscler Thromb Vasc Biol. 2004;24:1266-1271

Plaque Characteristics in Type I and II Diabetic

Subjects vs Nondiabetic Subjects

Burke AP, et al. Arterioscler Thromb Vasc Biol. 2004;24:1266-1271

Antiatherosclerosis Therapy in Diabetes

Beckman JA, et al. JAMA. 2002;287:2570-2581