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Abstract

목차

Ⅰ. Introduction 10

Ⅱ. Review of Literature 13

Ⅲ. Materials and Methods 24

LDL preparation and modification 24

Characterization of LDLs 24

Cell culture 24

MTT assay 25

Western blotting 25

Intracellular calcium release analysis 25

Biomolecular Interaction Analysis System 26

Data Analysis and Statistics 26

Ⅳ. Results 27

LDL characterization 27

Effects of LDLs on endothelial cell proliferation 27

Expression of COX-2 by glycated-LDL in endothelial cell 27

Intracellular calcium release of EC219 or HUVEC by native-, nonglycated- and glycated-LDL 32

Phosphorylation of ERK by native-, nonglycated- and glycated-LDL 32

Glycated-LDL-incuced ERK phosphorylation was modulated via Src kinase, Ras and MEK pathway 36

Phosphorylation of AKT by glycated-LDL 36

Glycated-LDL induce AKT activation in a PI3 Kinase-dependent pathway 36

Confirmation of IκB-α level by glycated-LDL 40

Comparison of binding rates of each LDL to β2 integrin(CD11c/CD18) 40

Ⅴ. Discussion 44

PART I 44

PART II 48

Ⅵ. References 50

Abstracts (in Korean) 56

감사의 글 58

그림목차

1. Events in atherosclerotic plaque formation 14

2. Participation of inflammation in all stages of atherosclerosis 15

3. Steps in atheroma formation and progression 16

4. Chemical reaction leading to the formation of advanced glycation endproducts 17

5. A scheme of signaling pathway connected with the proliferation and inflammation of endothelial cell by modified-LDL 19

6. Features of 2 integrins 21

7. Electrophoretic mobility of native-, nonglycated-and glycated-LDL by agarose gel electrophoresis 28

8. Comparision of lipid peroxidation of native-, nonglycated-and glycated-LDL by TBARS 29

9. Effect of native-, nonglycated- and glycated-LDL on EC219 proliferation 30

10. Time- or dose-dependent course of COX-2 expression by glycated-LDL in EC219 31

11. Intracellular calcium release of EC219 and HUVEC by native nonglycated-and glycated-LDL, 33

12. Induction of ERK phosphorylation by glycated-LDL in a time-dependent course 34

13. Effects of ERK phosphorylation by LDLs in a dose-dependent experiments 35

14. Glycated LDL-induced ERK phosphorylation was significantly inhibited by Src kinase, Ras and MEK inhibitor 37

15. Induction of AKT phosphorylation by glycated-LDL in EC219 38

16. Glycated-LDL-induced AKT phosphorylation was significantly inhibited by a Src kinase inhibitor and PI3-K inhibitor 39

17. Level of IκB-α by glycated-LDL in a time-dependent manner 41

18. Comparison of binding of native(N0)-, nonglycated(N10)-and glycated(G10)-LDL to β2 integrin(CD11c/CD18) 42

19. Binding rate of G60-LDL to β2 integrin(CD11c/CD18) 43

20. Proposed signal pathway of COX-2 expression by glycated-LDL on EC219 47

표목차

1. Major integrin pairing 22

2. Specific ligands of CD11/CD18(β2 integrin) 23