Skip to main content
Top
Published in: Diabetology International 1/2013

01-03-2013 | Review Article

The role of immunity and inflammation in the development of diabetic complications

Authors: Maria F. Lopes-Virella, Gabriel Virella

Published in: Diabetology International | Issue 1/2013

Login to get access

Abstract

Our group has carried out pivotal clinical studies on large cohorts of type 1 and type 2 diabetes to determine the impact of modified LDL-IC as well as inflammatory cytokines/adipokines and acute-phase reactant proteins in the development of diabetic complications. We have demonstrated that high levels of specific LDL modifications in circulating ICs correlate with increased risk for the development and progression of macrovascular disease, nephropathy, and retinopathy, frequently exceeding conventional risk factors in their predictive power. In cardiovascular disease, differences in the type of LDL modification and the stage of disease seem to lead to/predict different outcomes. The differences observed with ICs containing different types of modified LDL raises interesting questions about the role of the predominant LDL modification in the ICs and the cellular patterns of macrophage activation, survival, and apoptosis that result from LDL-IC ingestion. The differences observed in the predictive power of modified LDL-ICs at different stages of CVD development strongly suggest that modified LDL-ICs are causally related with the development of atherosclerosis and/or plaque instability. The association of cytokines/adipokines and acute-phase reactant proteins with the development of complications in type 1 diabetes is less strong than that observed with modified LDL-ICs and occurs at a later phase of the development of complications. In conclusion, the human humoral autoimmune response to modified forms of LDL is a typical adaptive response, with a switch to IgG synthesis and increasing antibody affinity that leads to the release of proinflammatory mediators, and it has unquestionable pathogenic characteristics.
Literature
1.
2.
go back to reference Miller YI, Choi SH, Fang L, Tsimikas S. Lipoprotein modification and macrophage uptake: role of pathologic cholesterol transport in atherogenesis. Subcell Biochem. 2010;51:229–51.PubMedCrossRef Miller YI, Choi SH, Fang L, Tsimikas S. Lipoprotein modification and macrophage uptake: role of pathologic cholesterol transport in atherogenesis. Subcell Biochem. 2010;51:229–51.PubMedCrossRef
3.
go back to reference Holvoet P. Endothelial dysfunction, oxidation of low-density lipoprotein, and cardiovascular disease. Ther Apher. 1999;3:287–93.PubMedCrossRef Holvoet P. Endothelial dysfunction, oxidation of low-density lipoprotein, and cardiovascular disease. Ther Apher. 1999;3:287–93.PubMedCrossRef
4.
go back to reference Lopes-Virella MF, Virella G. The role of immune and inflammatory processes in the development of macrovascular disease in diabetes. Front Biosci. 2003;8:s750–68.PubMedCrossRef Lopes-Virella MF, Virella G. The role of immune and inflammatory processes in the development of macrovascular disease in diabetes. Front Biosci. 2003;8:s750–68.PubMedCrossRef
5.
go back to reference Penn MS, Chisolm GM. Oxidized lipoproteins, altered cell function and atherosclerosis. Atherosclerosis. 1994;108:S21–9.PubMedCrossRef Penn MS, Chisolm GM. Oxidized lipoproteins, altered cell function and atherosclerosis. Atherosclerosis. 1994;108:S21–9.PubMedCrossRef
6.
go back to reference Henriksen T, Mahoney ME, Steinberg D. Enhanced macrophage degradation of biologically modified low density lipoprotein. Arteriosclerosis. 1983;3:149–58.PubMedCrossRef Henriksen T, Mahoney ME, Steinberg D. Enhanced macrophage degradation of biologically modified low density lipoprotein. Arteriosclerosis. 1983;3:149–58.PubMedCrossRef
7.
go back to reference Arai K, Kita T, Yokode M, Narumiya S, Kawai C. Multiple receptors for modified LDL in mouse peritoneal macrophages: different uptake mechanisms for acetylated and oxidized LDL. Biochem Biophys Res Commun. 1989;159:1375–9.PubMedCrossRef Arai K, Kita T, Yokode M, Narumiya S, Kawai C. Multiple receptors for modified LDL in mouse peritoneal macrophages: different uptake mechanisms for acetylated and oxidized LDL. Biochem Biophys Res Commun. 1989;159:1375–9.PubMedCrossRef
8.
go back to reference Endemann G, Stanton LW, Madden KS, Bryant CM, White RT, Protter AA. CD36 is a receptor for oxidized LDL. J Biol Chem. 1993;268:11811–8.PubMed Endemann G, Stanton LW, Madden KS, Bryant CM, White RT, Protter AA. CD36 is a receptor for oxidized LDL. J Biol Chem. 1993;268:11811–8.PubMed
9.
go back to reference Sparrow CP, Parthasarathy S, Steinberg D. A macrophage receptor that recognizes oxidized low density lipoprotein but not acetylated low density lipoprotein. J Biol Chem. 1989;264:2599–604.PubMed Sparrow CP, Parthasarathy S, Steinberg D. A macrophage receptor that recognizes oxidized low density lipoprotein but not acetylated low density lipoprotein. J Biol Chem. 1989;264:2599–604.PubMed
10.
go back to reference Hoff HF, O’Neil J, Chisolm GM, Cole TB, Quehenberger O, Esterbauer H, Jurgens G. Modification of low density lipoprotein with 4-hydroxynonenal induces uptake by macrophages. Arteriosclerosis. 1989;9:538–49.PubMedCrossRef Hoff HF, O’Neil J, Chisolm GM, Cole TB, Quehenberger O, Esterbauer H, Jurgens G. Modification of low density lipoprotein with 4-hydroxynonenal induces uptake by macrophages. Arteriosclerosis. 1989;9:538–49.PubMedCrossRef
11.
go back to reference Fogelman AM, Schechter I, Seager J, Hokom M, Child JS, Edwards PA. Malondialdehyde alteration of low density lipoproteins leads to cholesterol ester accumulation in human monocytes/macrophages. Proc Natl Acad Sci USA. 1980;77:2214–8.PubMedCrossRef Fogelman AM, Schechter I, Seager J, Hokom M, Child JS, Edwards PA. Malondialdehyde alteration of low density lipoproteins leads to cholesterol ester accumulation in human monocytes/macrophages. Proc Natl Acad Sci USA. 1980;77:2214–8.PubMedCrossRef
12.
go back to reference Hessler JR, Morel DW, Lewis LJ, Chisolm GM. Lipoprotein oxidation and lipoprotein-induced cytotoxicity. Arteriosclerosis. 1983;3:215–22.PubMedCrossRef Hessler JR, Morel DW, Lewis LJ, Chisolm GM. Lipoprotein oxidation and lipoprotein-induced cytotoxicity. Arteriosclerosis. 1983;3:215–22.PubMedCrossRef
13.
go back to reference Henriksen T, Evensen SA, Carlander B. Injury to human endothelial cells in culture induced by LDL. Scand J Clin Lab Investig. 1979;39:361–4.CrossRef Henriksen T, Evensen SA, Carlander B. Injury to human endothelial cells in culture induced by LDL. Scand J Clin Lab Investig. 1979;39:361–4.CrossRef
14.
go back to reference Rajavashisth TB, Andalibi A, Territo MC. Induction of endothelial cell expression of granulocyte and macrophage colony-stimulating factors by modified LDL. Nature. 1990;344:254–7.PubMedCrossRef Rajavashisth TB, Andalibi A, Territo MC. Induction of endothelial cell expression of granulocyte and macrophage colony-stimulating factors by modified LDL. Nature. 1990;344:254–7.PubMedCrossRef
15.
go back to reference Kugiyama K, Sakamoto T, Musumi I, Sugiyama S, Ohgushi M, Ogawa H, Horiguchi M, Yasue H. Transferrable lipids in oxidized LDL stimulate PAI-1 and inhibit tPA release from endothelial cells. Circ Res. 1993;73:335–43.PubMedCrossRef Kugiyama K, Sakamoto T, Musumi I, Sugiyama S, Ohgushi M, Ogawa H, Horiguchi M, Yasue H. Transferrable lipids in oxidized LDL stimulate PAI-1 and inhibit tPA release from endothelial cells. Circ Res. 1993;73:335–43.PubMedCrossRef
16.
go back to reference Quinn MT, Parthasarathy S, Fong LG, Steinberg D. Oxidatively modified low density lipoproteins: a potential role in recruitment and retention of monocyte/macrophages during atherogenesis. Proc Natl Acad Sci USA. 1987;84:2995–8.PubMedCrossRef Quinn MT, Parthasarathy S, Fong LG, Steinberg D. Oxidatively modified low density lipoproteins: a potential role in recruitment and retention of monocyte/macrophages during atherogenesis. Proc Natl Acad Sci USA. 1987;84:2995–8.PubMedCrossRef
17.
go back to reference Berliner JA, Territo MC, Sevanian A, Raimin S, Kim JA, Bamshad B, Ester-son M, Fogelman AM. Minimally modified low density lipoprotein stimulates monocyte endothelial interactions. J Clin Investig. 1990;85:1260–6.PubMedCrossRef Berliner JA, Territo MC, Sevanian A, Raimin S, Kim JA, Bamshad B, Ester-son M, Fogelman AM. Minimally modified low density lipoprotein stimulates monocyte endothelial interactions. J Clin Investig. 1990;85:1260–6.PubMedCrossRef
18.
go back to reference Kume N, Cybulsky MI, Gimbrone MAJ. Lysophosphatidyl-choline, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells. J Clin Investig. 1992;90:1138–44.PubMedCrossRef Kume N, Cybulsky MI, Gimbrone MAJ. Lysophosphatidyl-choline, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells. J Clin Investig. 1992;90:1138–44.PubMedCrossRef
19.
go back to reference Kahn BV, Parthasarathy SS, Alexander RW, Medford RM. Modified LDL and its constituents augment cytokine-activated vascular cell adhesion molecule-1 gene expression in human vascular endothelial cells. J Clin Investig. 1995;95:1262–70.CrossRef Kahn BV, Parthasarathy SS, Alexander RW, Medford RM. Modified LDL and its constituents augment cytokine-activated vascular cell adhesion molecule-1 gene expression in human vascular endothelial cells. J Clin Investig. 1995;95:1262–70.CrossRef
20.
go back to reference Takei A, Huang Y, Lopes-Virella MF. Expression of adhesion molecules by human endothelial cells exposed to oxidized low density lipoprotein. Influences of degree of oxidation and location of oxidized LDL. Atherosclerosis. 2001;154:79–86.PubMedCrossRef Takei A, Huang Y, Lopes-Virella MF. Expression of adhesion molecules by human endothelial cells exposed to oxidized low density lipoprotein. Influences of degree of oxidation and location of oxidized LDL. Atherosclerosis. 2001;154:79–86.PubMedCrossRef
21.
go back to reference Vlassara H, Cai W, Crandall J, Goldberg T, Oberstein R, Dardaine V, Peppa M, Rayfield EJ. Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy. Proc Natl Acad Sci USA. 2002;99:15596–601.PubMedCrossRef Vlassara H, Cai W, Crandall J, Goldberg T, Oberstein R, Dardaine V, Peppa M, Rayfield EJ. Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy. Proc Natl Acad Sci USA. 2002;99:15596–601.PubMedCrossRef
22.
go back to reference Wendt T, Bucciarelli L, Qu W, Lu Y, Yan SF, Stern DM, Schmidt AM. Receptor for advanced glycation endproducts (RAGE) and vascular inflammation: insights into the pathogenesis of macrovascular complications in diabetes. Curr Atheroscler Rep. 2002;4:228–37.PubMedCrossRef Wendt T, Bucciarelli L, Qu W, Lu Y, Yan SF, Stern DM, Schmidt AM. Receptor for advanced glycation endproducts (RAGE) and vascular inflammation: insights into the pathogenesis of macrovascular complications in diabetes. Curr Atheroscler Rep. 2002;4:228–37.PubMedCrossRef
23.
go back to reference Vlassara H, Bucala R, Striker L. Pathogenic effects of advanced glycosylation: biochemical, biologic, and clinical implications for diabetes and aging. Lab Investig. 1994;70:138–51.PubMed Vlassara H, Bucala R, Striker L. Pathogenic effects of advanced glycosylation: biochemical, biologic, and clinical implications for diabetes and aging. Lab Investig. 1994;70:138–51.PubMed
24.
go back to reference Schmidt AM, Hori O, Chen JX, Li JF, Crandall J, Zhang J, Cao R, Yan SD, Brett J, Stern D. Advanced glycation endproducts interacting with their endothelial receptor induce expression of vascular cell adhesion molecule-1 (VCAM-1) in cultured human endothelial cells and in mice. A potential mechanism for the accelerated vasculopathy of diabetes. J Clin Investig. 1995;96:1395–403.PubMedCrossRef Schmidt AM, Hori O, Chen JX, Li JF, Crandall J, Zhang J, Cao R, Yan SD, Brett J, Stern D. Advanced glycation endproducts interacting with their endothelial receptor induce expression of vascular cell adhesion molecule-1 (VCAM-1) in cultured human endothelial cells and in mice. A potential mechanism for the accelerated vasculopathy of diabetes. J Clin Investig. 1995;96:1395–403.PubMedCrossRef
25.
go back to reference De Boer OJ, van der Wal AC, Verhagen CE, Becker AE. Cytokine secretion profiles of cloned T cells from human aortic atherosclerotic plaques. J Pathol. 1999;188:174–9.PubMedCrossRef De Boer OJ, van der Wal AC, Verhagen CE, Becker AE. Cytokine secretion profiles of cloned T cells from human aortic atherosclerotic plaques. J Pathol. 1999;188:174–9.PubMedCrossRef
26.
go back to reference Bucciarelli LG, Wendt T, Qu W, Lu Y, Lalla E, Rong LL, Goova MT, Moser B, Kislinger T, Lee DC, Kashyap Y, Stern DM, Schmidt AM. RAGE blockade stabilizes established atherosclerosis in diabetic apolipoprotein E-null mice. Circulation. 2002;106:2827–35.PubMedCrossRef Bucciarelli LG, Wendt T, Qu W, Lu Y, Lalla E, Rong LL, Goova MT, Moser B, Kislinger T, Lee DC, Kashyap Y, Stern DM, Schmidt AM. RAGE blockade stabilizes established atherosclerosis in diabetic apolipoprotein E-null mice. Circulation. 2002;106:2827–35.PubMedCrossRef
27.
go back to reference Steinbrecher UP, Fisher M, Witztum JL, Curtiss LK. Immunogenicity of homologous low density lipoprotein after methylation, ethylation, acetylation, or carbamylation: generation of antibodies specific for derivatized lysine. J Lipid Res. 1984;25:1109–16.PubMed Steinbrecher UP, Fisher M, Witztum JL, Curtiss LK. Immunogenicity of homologous low density lipoprotein after methylation, ethylation, acetylation, or carbamylation: generation of antibodies specific for derivatized lysine. J Lipid Res. 1984;25:1109–16.PubMed
28.
go back to reference Steinbrecher UP. Oxidation of human low density lipoprotein results in derivatization of lysine residues of apolipoprotein B by lipid peroxide decomposition products. J Biol Chem. 1987;262:3603–8.PubMed Steinbrecher UP. Oxidation of human low density lipoprotein results in derivatization of lysine residues of apolipoprotein B by lipid peroxide decomposition products. J Biol Chem. 1987;262:3603–8.PubMed
29.
go back to reference Palinski W, Yla-Herttuala S, Rosenfeld ME, Butler SW, Socher SA, Parthasarathy S, Curtiss LK, Witztum JL. Antisera and monoclonal antibodies specific for epitopes generated during oxidative modification of low density lipoprotein. Arteriosclerosis. 1990;10:325–35.PubMedCrossRef Palinski W, Yla-Herttuala S, Rosenfeld ME, Butler SW, Socher SA, Parthasarathy S, Curtiss LK, Witztum JL. Antisera and monoclonal antibodies specific for epitopes generated during oxidative modification of low density lipoprotein. Arteriosclerosis. 1990;10:325–35.PubMedCrossRef
30.
go back to reference Yla-Herttuala S, Palinski W, Butler S, Picard S, Steinberg D, Witztum JL. Rabbit and human atherosclerotic lesions contain IgG that recognizes epitopes of oxidized LDL. Arterioscler Thromb. 1994;14:32–40.PubMedCrossRef Yla-Herttuala S, Palinski W, Butler S, Picard S, Steinberg D, Witztum JL. Rabbit and human atherosclerotic lesions contain IgG that recognizes epitopes of oxidized LDL. Arterioscler Thromb. 1994;14:32–40.PubMedCrossRef
31.
go back to reference Mironova M, Virella G, Lopes-Virella MF. Isolation and characterization of human antioxidized LDL autoantibodies. Arterioscler Thromb Vasc Biol. 1996;16:222–9.PubMedCrossRef Mironova M, Virella G, Lopes-Virella MF. Isolation and characterization of human antioxidized LDL autoantibodies. Arterioscler Thromb Vasc Biol. 1996;16:222–9.PubMedCrossRef
32.
go back to reference Virella G, Koskinen S, Krings G, Onorato JM, Thorpe SR, Lopes-Virella M. Immunochemical characterization of purified human oxidized low-density lipoprotein antibodies. Clin Immunol. 2000;95:135–44.PubMedCrossRef Virella G, Koskinen S, Krings G, Onorato JM, Thorpe SR, Lopes-Virella M. Immunochemical characterization of purified human oxidized low-density lipoprotein antibodies. Clin Immunol. 2000;95:135–44.PubMedCrossRef
33.
go back to reference Lopes-Virella MF, McHenry MB, Lipsitz S, Yim E, Wilson PF, Lackland DT, Lyons T, Jenkins AJ, Virella G. Immune complexes containing modified lipoproteins are related to the progression of internal carotid intima-media thickness in patients with type 1 diabetes. Atherosclerosis. 2007;190:359–69.PubMedCrossRef Lopes-Virella MF, McHenry MB, Lipsitz S, Yim E, Wilson PF, Lackland DT, Lyons T, Jenkins AJ, Virella G. Immune complexes containing modified lipoproteins are related to the progression of internal carotid intima-media thickness in patients with type 1 diabetes. Atherosclerosis. 2007;190:359–69.PubMedCrossRef
34.
go back to reference Lopes-Virella MF, Virella G. Clinical significance of the humoral immune response to modified LDL. Clin Immunol. 2010;134:55–65.PubMedCrossRef Lopes-Virella MF, Virella G. Clinical significance of the humoral immune response to modified LDL. Clin Immunol. 2010;134:55–65.PubMedCrossRef
35.
go back to reference Lopes-Virella MF, Hunt KJ, Baker NL, Lachin J, Nathan DM, Virella G. The levels of oxidized LDL and AGE-LDL in circulating immune complexes are strongly associated with increased levels of carotid intima-media thickness and its progression in type 1 diabetes. Diabetes. 2011;60:582–9.PubMedCrossRef Lopes-Virella MF, Hunt KJ, Baker NL, Lachin J, Nathan DM, Virella G. The levels of oxidized LDL and AGE-LDL in circulating immune complexes are strongly associated with increased levels of carotid intima-media thickness and its progression in type 1 diabetes. Diabetes. 2011;60:582–9.PubMedCrossRef
36.
go back to reference Saad AF, Virella G, Chassereau C, Boackle RJ, Lopes-Virella MF. OxLDL immune complexes activate complement and induce cytokine production by MonoMac 6 cells and human macrophages. J Lipid Res. 2006;47:1975–83.PubMedCrossRef Saad AF, Virella G, Chassereau C, Boackle RJ, Lopes-Virella MF. OxLDL immune complexes activate complement and induce cytokine production by MonoMac 6 cells and human macrophages. J Lipid Res. 2006;47:1975–83.PubMedCrossRef
37.
go back to reference Virella G, Atchley DH, Koskinen S, Zheng D, Lopes-Virella M. Pro-atherogenic and pro-inflammatory properties of immune complexes prepared with purified human oxLDL antibodies and human oxLDL. Clin Immunol. 2002;105:81–92.PubMedCrossRef Virella G, Atchley DH, Koskinen S, Zheng D, Lopes-Virella M. Pro-atherogenic and pro-inflammatory properties of immune complexes prepared with purified human oxLDL antibodies and human oxLDL. Clin Immunol. 2002;105:81–92.PubMedCrossRef
38.
go back to reference Virella G, Carter RE, Saad A, Crosswell EG, Game BA, Lopes-Virella MF. Distribution of IgM and IgG antibodies to oxidized LDL in immune complexes isolated from patients with type 1 diabetes and its relationship with nephropathy. Clin Immunol. 2008;127:394–400.PubMedCrossRef Virella G, Carter RE, Saad A, Crosswell EG, Game BA, Lopes-Virella MF. Distribution of IgM and IgG antibodies to oxidized LDL in immune complexes isolated from patients with type 1 diabetes and its relationship with nephropathy. Clin Immunol. 2008;127:394–400.PubMedCrossRef
39.
go back to reference Atchley DH, Lopes-Virella MF, Zheng D, Virella G. Oxidized LDL-anti-oxidized LDL immune complexes and diabetic nephropathy. Diabetologia. 2002;45:1562–71.PubMedCrossRef Atchley DH, Lopes-Virella MF, Zheng D, Virella G. Oxidized LDL-anti-oxidized LDL immune complexes and diabetic nephropathy. Diabetologia. 2002;45:1562–71.PubMedCrossRef
40.
go back to reference Virella G, Thorpe S, Alderson NL, Derrick MB, Chassereau C, Rhett JM, Lopes-Virella MF. Definition of the immunogenic forms of modified human LDL recognized by human autoantibodies and by rabbit hyperimmune antibodies. J Lipid Res. 2004;45:1859–67.PubMedCrossRef Virella G, Thorpe S, Alderson NL, Derrick MB, Chassereau C, Rhett JM, Lopes-Virella MF. Definition of the immunogenic forms of modified human LDL recognized by human autoantibodies and by rabbit hyperimmune antibodies. J Lipid Res. 2004;45:1859–67.PubMedCrossRef
41.
go back to reference Virella G, Derrick MB, Pate V, Chassereau C, Thorpe SR, Lopes-Virella MF. Development of capture assays for different modifications of human low-density lipoprotein. Clin Diagn Lab Immunol. 2005;12:68–75.PubMed Virella G, Derrick MB, Pate V, Chassereau C, Thorpe SR, Lopes-Virella MF. Development of capture assays for different modifications of human low-density lipoprotein. Clin Diagn Lab Immunol. 2005;12:68–75.PubMed
42.
go back to reference Lopes-Virella MF, Baker NL, Hunt KJ, Lyons TJ, Jenkins AJ, Virella G. High concentrations of AGE-LDL and oxidized LDL in circulating immune complexes are associated with progression of retinopathy in type 1 diabetes. Diabetes Care. 2012;35:1333–40.PubMedCrossRef Lopes-Virella MF, Baker NL, Hunt KJ, Lyons TJ, Jenkins AJ, Virella G. High concentrations of AGE-LDL and oxidized LDL in circulating immune complexes are associated with progression of retinopathy in type 1 diabetes. Diabetes Care. 2012;35:1333–40.PubMedCrossRef
43.
go back to reference Lopes-Virella MF, Carter RE, Baker NL, Lachin J, Virella G. High levels of oxidized LDL in circulating immune complexes are associated with increased odds of developing abnormal albuminuria in Type 1 diabetes. Nephrol Dial Transplant. 2012;27:1416–23.PubMedCrossRef Lopes-Virella MF, Carter RE, Baker NL, Lachin J, Virella G. High levels of oxidized LDL in circulating immune complexes are associated with increased odds of developing abnormal albuminuria in Type 1 diabetes. Nephrol Dial Transplant. 2012;27:1416–23.PubMedCrossRef
44.
go back to reference Lopes-Virella MF, Baker NL, Hunt KJ, Lachin J, Nathan D, Virella G. Oxidized LDL immune complexes and coronary artery calcification in type 1 diabetes. Atherosclerosis. 2011;214:462–7.PubMedCrossRef Lopes-Virella MF, Baker NL, Hunt KJ, Lachin J, Nathan D, Virella G. Oxidized LDL immune complexes and coronary artery calcification in type 1 diabetes. Atherosclerosis. 2011;214:462–7.PubMedCrossRef
45.
go back to reference Lopes-Virella MF, Baker NL, Hunt KJ, Moritz T, Virella G, VADT Investigators. The levels of MDA-LDL in circulating immune complexes predict myocardial infarction in the VADT study. Atherosclerosis. 2012;224:526–31.PubMedCrossRef Lopes-Virella MF, Baker NL, Hunt KJ, Moritz T, Virella G, VADT Investigators. The levels of MDA-LDL in circulating immune complexes predict myocardial infarction in the VADT study. Atherosclerosis. 2012;224:526–31.PubMedCrossRef
46.
go back to reference Holvoet P, Perez G, Zhao Z, Brouwers E, Bernar H, Collen D. Malondialdehyde-modified low density lipoproteins in patients with atherosclerotic disease. J Clin Investig. 1995;95:2611–9.PubMedCrossRef Holvoet P, Perez G, Zhao Z, Brouwers E, Bernar H, Collen D. Malondialdehyde-modified low density lipoproteins in patients with atherosclerotic disease. J Clin Investig. 1995;95:2611–9.PubMedCrossRef
47.
go back to reference Holvoet P, Vanhaecke J, Janssens S, Van de Werf F, Collen D. Oxidized LDL and malondialdehyde-modified LDL in patients with acute coronary syndromes and stable coronary artery disease. Circulation. 1998;98:1487–94.PubMedCrossRef Holvoet P, Vanhaecke J, Janssens S, Van de Werf F, Collen D. Oxidized LDL and malondialdehyde-modified LDL in patients with acute coronary syndromes and stable coronary artery disease. Circulation. 1998;98:1487–94.PubMedCrossRef
48.
49.
go back to reference Shah PK. Pathophysiology of coronary thrombosis: role of plaque rupture and plaque erosion. Prog Cardiovasc Dis. 2002;44:357–68.PubMedCrossRef Shah PK. Pathophysiology of coronary thrombosis: role of plaque rupture and plaque erosion. Prog Cardiovasc Dis. 2002;44:357–68.PubMedCrossRef
51.
go back to reference Moreno PR, Murcia AM, Palacios IF, Leon MN, Bernardi VH, Fuster V, Fallon JT. Coronary composition and macrophage infiltration in atherectomy specimens from patients with diabetes mellitus. Circulation. 2000;102:2180–4.PubMedCrossRef Moreno PR, Murcia AM, Palacios IF, Leon MN, Bernardi VH, Fuster V, Fallon JT. Coronary composition and macrophage infiltration in atherectomy specimens from patients with diabetes mellitus. Circulation. 2000;102:2180–4.PubMedCrossRef
52.
go back to reference Galis ZS, Sukhova GK, Lark MW, Libby P. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Investig. 1994;94:2493–503.PubMedCrossRef Galis ZS, Sukhova GK, Lark MW, Libby P. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Investig. 1994;94:2493–503.PubMedCrossRef
53.
go back to reference Seimon T, Tabas I. Mechanisms and consequences of macrophage apoptosis in atherosclerosis. J Lipid Res. 2009;50(Suppl):S382–7.PubMedCrossRef Seimon T, Tabas I. Mechanisms and consequences of macrophage apoptosis in atherosclerosis. J Lipid Res. 2009;50(Suppl):S382–7.PubMedCrossRef
54.
go back to reference Lopes-Virella MF, Griffith RL, Shunk KA, Virella GT. Enhanced uptake and impaired intracellular metabolism of low density lipoprotein complexed with anti-low density lipoprotein antibodies. Arterioscler Thromb. 1991;11:1356–67.PubMedCrossRef Lopes-Virella MF, Griffith RL, Shunk KA, Virella GT. Enhanced uptake and impaired intracellular metabolism of low density lipoprotein complexed with anti-low density lipoprotein antibodies. Arterioscler Thromb. 1991;11:1356–67.PubMedCrossRef
55.
go back to reference Lopes-Virella MF, Binzafar N, Rackley S, Takei A, La Via M, Virella G. The uptake of LDL-IC by human macrophages: predominant involvement of the Fc gamma RI receptor. Atherosclerosis. 1997;135:161–70.PubMedCrossRef Lopes-Virella MF, Binzafar N, Rackley S, Takei A, La Via M, Virella G. The uptake of LDL-IC by human macrophages: predominant involvement of the Fc gamma RI receptor. Atherosclerosis. 1997;135:161–70.PubMedCrossRef
56.
go back to reference Oksjoki R, Kovanen PT, Lindstedt KA, Jansson B, Pentikainen MO. OxLDL-IgG immune complexes induce survival of human monocytes. Arterioscler Thromb Vasc Biol. 2006;26:576–83.PubMedCrossRef Oksjoki R, Kovanen PT, Lindstedt KA, Jansson B, Pentikainen MO. OxLDL-IgG immune complexes induce survival of human monocytes. Arterioscler Thromb Vasc Biol. 2006;26:576–83.PubMedCrossRef
57.
go back to reference de Boer OJ, van der Wal AC, Houtkamp MA, Ossewaarde JM, Teeling P, Becker AE. Unstable atherosclerotic plaques contain T-cells that respond to Chlamydia pneumoniae. Cardiovasc Res. 2000;48:402–8.PubMedCrossRef de Boer OJ, van der Wal AC, Houtkamp MA, Ossewaarde JM, Teeling P, Becker AE. Unstable atherosclerotic plaques contain T-cells that respond to Chlamydia pneumoniae. Cardiovasc Res. 2000;48:402–8.PubMedCrossRef
58.
go back to reference Lim WS, Timmins JM, Seimon TA, Sadler A, Kolodgie FD, Virmani R, Tabas I. Signal transducer and activator of transcription-1 is critical for apoptosis in macrophages subjected to endoplasmic reticulum stress in vitro and in advanced atherosclerotic lesions in vivo. Circulation. 2008;117:940–51.PubMedCrossRef Lim WS, Timmins JM, Seimon TA, Sadler A, Kolodgie FD, Virmani R, Tabas I. Signal transducer and activator of transcription-1 is critical for apoptosis in macrophages subjected to endoplasmic reticulum stress in vitro and in advanced atherosclerotic lesions in vivo. Circulation. 2008;117:940–51.PubMedCrossRef
59.
go back to reference Hundal RS, Gomez-Munoz A, Kong JY, Salh BS, Marotta A, Duronio V, Steinbrecher UP. Oxidized low density lipoprotein inhibits macrophage apoptosis by blocking ceramide generation, thereby maintaining protein kinase B activation and Bcl-XL levels. J Biol Chem. 2003;278:24399–408.PubMedCrossRef Hundal RS, Gomez-Munoz A, Kong JY, Salh BS, Marotta A, Duronio V, Steinbrecher UP. Oxidized low density lipoprotein inhibits macrophage apoptosis by blocking ceramide generation, thereby maintaining protein kinase B activation and Bcl-XL levels. J Biol Chem. 2003;278:24399–408.PubMedCrossRef
60.
go back to reference Tohyama Y, Yamamura H. Protein tyrosine kinase, syk: a key player in phagocytic cells. J Biochem. 2009;145:267–73.PubMedCrossRef Tohyama Y, Yamamura H. Protein tyrosine kinase, syk: a key player in phagocytic cells. J Biochem. 2009;145:267–73.PubMedCrossRef
61.
go back to reference Crowley MT, Costello PS, Fitzer-Attas CJ, Turner M, Meng F, Lowell C, Tybulewicz VL, DeFranco AL. A critical role for Syk in signal transduction and phagocytosis mediated by Fcgamma receptors on macrophages. J Exp Med. 1997;186:1027–39.PubMedCrossRef Crowley MT, Costello PS, Fitzer-Attas CJ, Turner M, Meng F, Lowell C, Tybulewicz VL, DeFranco AL. A critical role for Syk in signal transduction and phagocytosis mediated by Fcgamma receptors on macrophages. J Exp Med. 1997;186:1027–39.PubMedCrossRef
62.
go back to reference Huang Y, Jaffa A, Koskinen S, Takei A, Lopes-Virella MF. Oxidized LDL-containing immune complexes induce Fc gamma receptor I-mediated mitogen-activated protein kinase activation in THP-1 macrophages. Arterioscler Thromb Vasc Biol. 1999;19:1600–7.PubMedCrossRef Huang Y, Jaffa A, Koskinen S, Takei A, Lopes-Virella MF. Oxidized LDL-containing immune complexes induce Fc gamma receptor I-mediated mitogen-activated protein kinase activation in THP-1 macrophages. Arterioscler Thromb Vasc Biol. 1999;19:1600–7.PubMedCrossRef
63.
go back to reference Luo Y, Pollard JW, Casadevall A. Fcgamma receptor cross-linking stimulates cell proliferation of macrophages via the ERK pathway. J Biol Chem. 2010;285:4232–42.PubMedCrossRef Luo Y, Pollard JW, Casadevall A. Fcgamma receptor cross-linking stimulates cell proliferation of macrophages via the ERK pathway. J Biol Chem. 2010;285:4232–42.PubMedCrossRef
64.
go back to reference Chen JH, Riazy M, Wang SW, Dai JM, Duronio V, Steinbrecher UP. Sphingosine kinase regulates oxidized low density lipoprotein-mediated calcium oscillations and macrophage survival. J Lipid Res. 2010;51:991–8.PubMedCrossRef Chen JH, Riazy M, Wang SW, Dai JM, Duronio V, Steinbrecher UP. Sphingosine kinase regulates oxidized low density lipoprotein-mediated calcium oscillations and macrophage survival. J Lipid Res. 2010;51:991–8.PubMedCrossRef
65.
go back to reference Datta SR, Brunet A, Greenberg ME. Cellular survival: a play in three Akts. Genes Dev. 1999;13:2905–27.PubMedCrossRef Datta SR, Brunet A, Greenberg ME. Cellular survival: a play in three Akts. Genes Dev. 1999;13:2905–27.PubMedCrossRef
66.
go back to reference Lebman DA, Spiegel S. Cross-talk at the crossroads of sphingosine-1-phosphate, growth factors, and cytokine signaling. J Lipid Res. 2008;49:1388–94.PubMedCrossRef Lebman DA, Spiegel S. Cross-talk at the crossroads of sphingosine-1-phosphate, growth factors, and cytokine signaling. J Lipid Res. 2008;49:1388–94.PubMedCrossRef
67.
go back to reference Al Gadban MM, Smith KJ, Soodavar F, Piansay C, Chassereau C, Twal WO, Klein RL, Virella G, Lopes-Virella MF, Hammad SM. Differential trafficking of oxidized LDL and oxidized LDL immune complexes in macrophages: impact on oxidative stress. PLoS One. 2010;5(9):e12534. doi:10.1371/journal.pone.0012534. Al Gadban MM, Smith KJ, Soodavar F, Piansay C, Chassereau C, Twal WO, Klein RL, Virella G, Lopes-Virella MF, Hammad SM. Differential trafficking of oxidized LDL and oxidized LDL immune complexes in macrophages: impact on oxidative stress. PLoS One. 2010;5(9):e12534. doi:10.​1371/​journal.​pone.​0012534.
68.
go back to reference Smith KJ, Twal WO, Soodavar F, Virella G, Lopes-Virella MF, Hammad SM. Heat shock protein 70B′ (HSP70B′) expression and release in response to human oxidized low density lipoprotein immune complexes in macrophages. J Biol Chem. 2010;285:15985–93.PubMedCrossRef Smith KJ, Twal WO, Soodavar F, Virella G, Lopes-Virella MF, Hammad SM. Heat shock protein 70B′ (HSP70B′) expression and release in response to human oxidized low density lipoprotein immune complexes in macrophages. J Biol Chem. 2010;285:15985–93.PubMedCrossRef
69.
go back to reference Hammad SM, Twal WO, Barth JL, Smith KJ, Saad AF, Virella G, Argraves WS, Lopes-Virella MF. Oxidized LDL immune complexes and oxidized LDL differentially affect the expression of genes involved with inflammation and survival in human U937 monocytic cells. Atherosclerosis. 2009;202:394–404.PubMedCrossRef Hammad SM, Twal WO, Barth JL, Smith KJ, Saad AF, Virella G, Argraves WS, Lopes-Virella MF. Oxidized LDL immune complexes and oxidized LDL differentially affect the expression of genes involved with inflammation and survival in human U937 monocytic cells. Atherosclerosis. 2009;202:394–404.PubMedCrossRef
70.
go back to reference Viita H, Narvanen O, Yla-Herttuala S. Different apolipoprotein B breakdown patterns in models of oxidized low density lipoprotein. Life Sci. 1999;65:783–93.PubMedCrossRef Viita H, Narvanen O, Yla-Herttuala S. Different apolipoprotein B breakdown patterns in models of oxidized low density lipoprotein. Life Sci. 1999;65:783–93.PubMedCrossRef
71.
go back to reference Hoff HF, Zyromski N, Armstrong D, O’Neil J. Aggregation as well as chemical modification of LDL during oxidation is responsible for poor processing in macrophages. J Lipid Res. 1993;34:1919–29.PubMed Hoff HF, Zyromski N, Armstrong D, O’Neil J. Aggregation as well as chemical modification of LDL during oxidation is responsible for poor processing in macrophages. J Lipid Res. 1993;34:1919–29.PubMed
72.
go back to reference Koenig W, Khuseyinova N. Biomarkers of atherosclerotic plaque instability and rupture. Arterioscler Thromb Vasc Biol. 2007;27:15–26.PubMedCrossRef Koenig W, Khuseyinova N. Biomarkers of atherosclerotic plaque instability and rupture. Arterioscler Thromb Vasc Biol. 2007;27:15–26.PubMedCrossRef
73.
go back to reference Colley KJ, Wolfert RL, Cobble ME. Lipoprotein associated phospholipase A(2): role in atherosclerosis and utility as a biomarker for cardiovascular risk. EPMA J. 2011;2:27–38.PubMedCrossRef Colley KJ, Wolfert RL, Cobble ME. Lipoprotein associated phospholipase A(2): role in atherosclerosis and utility as a biomarker for cardiovascular risk. EPMA J. 2011;2:27–38.PubMedCrossRef
74.
go back to reference Loftus IM, Naylor AR, Bell PR, Thompson MM. Plasma MMP-9—a marker of carotid plaque instability. Eur J Vasc Endovasc Surg. 2001;21:17–21.PubMedCrossRef Loftus IM, Naylor AR, Bell PR, Thompson MM. Plasma MMP-9—a marker of carotid plaque instability. Eur J Vasc Endovasc Surg. 2001;21:17–21.PubMedCrossRef
75.
go back to reference Pelisek J, Rudelius M, Zepper P, Poppert H, Reeps C, Schuster T, Eckstein HH. Multiple biological predictors for vulnerable carotid lesions. Cerebrovasc Dis. 2009;28:601–10.PubMedCrossRef Pelisek J, Rudelius M, Zepper P, Poppert H, Reeps C, Schuster T, Eckstein HH. Multiple biological predictors for vulnerable carotid lesions. Cerebrovasc Dis. 2009;28:601–10.PubMedCrossRef
76.
go back to reference Hoke M, Schillinger M, Zorn G, Wonnerth A, Amighi J, Mlekusch W, Speidl W, Maurer G, Koppensteiner R, Minar E, Wojta J, Niessner A. The prognostic impact of soluble apoptosis-stimulating fragment on mortality in patients with carotid atherosclerosis. Stroke. 2011;42:2465–70.PubMedCrossRef Hoke M, Schillinger M, Zorn G, Wonnerth A, Amighi J, Mlekusch W, Speidl W, Maurer G, Koppensteiner R, Minar E, Wojta J, Niessner A. The prognostic impact of soluble apoptosis-stimulating fragment on mortality in patients with carotid atherosclerosis. Stroke. 2011;42:2465–70.PubMedCrossRef
77.
go back to reference Blanco-Colio LM, Martin-Ventura JL, Tunon J, Garcia-Camarero T, Berrazueta JR, Egido J. Soluble Fas ligand plasma levels are associated with forearm reactive hyperemia in subjects with coronary artery disease: a novel biomarker of endothelial function? Atherosclerosis. 2008;201:407–12.PubMedCrossRef Blanco-Colio LM, Martin-Ventura JL, Tunon J, Garcia-Camarero T, Berrazueta JR, Egido J. Soluble Fas ligand plasma levels are associated with forearm reactive hyperemia in subjects with coronary artery disease: a novel biomarker of endothelial function? Atherosclerosis. 2008;201:407–12.PubMedCrossRef
Metadata
Title
The role of immunity and inflammation in the development of diabetic complications
Authors
Maria F. Lopes-Virella
Gabriel Virella
Publication date
01-03-2013
Publisher
Springer Japan
Published in
Diabetology International / Issue 1/2013
Print ISSN: 2190-1678
Electronic ISSN: 2190-1686
DOI
https://doi.org/10.1007/s13340-013-0105-3

Other articles of this Issue 1/2013

Diabetology International 1/2013 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine