Anti-modified LDL antibodies, LDL-containing immune complexes, and susceptibility of LDL to in vitro oxidation in patients with type 2 diabetes.

Mironova, Marina; Klein, Richard L.; Virella, Gabriel; Lopes‐Virella, Maria F.

doi:10.2337/diabetes.49.6.1033

Cited by 87 publications

(61 citation statements)

References 50 publications

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“…The atherogenic and pro-inflammatory properties of LDL-IC in humans have also been established by in vitro studies of the properties of LDL-IC, either isolated from patient's sera by polyethylene glycol [PEG] precipitation [39,[50][51][52][53] or prepared in vitro with rabbit antibodies or with isolated human antibodies. The exposure of human monocyte-derived macrophages to mLDL-IC isolated from the sera of diabetic patients and from some healthy controls with high levels of circulating LDL-IC is followed by intracellular accumulation of cholesterol and cholesterol esters [39,52,54].…”

Section: The Pathogenic Role Of Immune Complexes Formed By Oxldl and mentioning

confidence: 99%

“…The exposure of human monocyte-derived macrophages to mLDL-IC isolated from the sera of diabetic patients and from some healthy controls with high levels of circulating LDL-IC is followed by intracellular accumulation of cholesterol and cholesterol esters [39,52,54]. At the same time, the macrophages ingesting isolated LDL-IC become activated and release proinflammatory cytokines, and oxygen active radicals [55].…”

Section: The Pathogenic Role Of Immune Complexes Formed By Oxldl and mentioning

confidence: 99%

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Atherogenesis and the humoral immune response to modified lipoproteins

Virella¹,

Lopes‐Virella²

2008

Atherosclerosis

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Modified forms of LDL are immunogenic and activate both cell-mediated and humoral immune responses. Both types of responses are pro-inflammatory and are probably primary players in the perpetuation of the chronic inflammatory reaction characteristic of atherosclerosis. The immunologic response to modified LDL can be directed to MHC-II-associated peptides in the case of T helper cells, and to a variety of epitopes -modified lysine groups, modified phospholipids, proteins that become associated with oxidized LDL (such as β2GP1) -in the case of B cell responses. T cell activation is likely to play a major role through cross-activation of macrophages. Humoral responses to modified LDL are pathogenic as a consequence of the formation of antigen-antibody complexes containing modified LDL and IgG antibodies. Those immune complexes induce cholesterol ester accumulation in macrophages and macrophage-like cells, and induce the release of proinflammatory cytokines, chemokines, oxygen active radicals, and matrix metalloproteinases from those cells. There is no conclusive evidence supporting a protective role for IgM antibodies in humans, possibly because autoantibodies to modified lipoproteins are predominantly of the IgG isotype.

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Section: The Pathogenic Role Of Immune Complexes Formed By Oxldl and mentioning

confidence: 99%

Section: The Pathogenic Role Of Immune Complexes Formed By Oxldl and mentioning

confidence: 99%

Atherogenesis and the humoral immune response to modified lipoproteins

Virella¹,

Lopes‐Virella²

2008

Atherosclerosis

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“…Thus, the results indicate that NNSE may also possess insulin-like action by virtue of the ability to lower the lipid levels. The present study reveals that the levels of serum lipid profiles are usually raised in diabetic rats, and such an elevation represents a risk factor for coronary heart diseases (CAD) [48]. Lowering the serum lipid level through dietary or drug therapy seems to be associated with a decrease in the risk of cardiovascular disease (CVD) [49].…”

Section: Effect Of Nnse On Antioxidant Enzymesmentioning

confidence: 99%

Antidiabetic and Antihyperlipidaemic Activity of Nelumbo Nucifera Gaertn Ethanol Seed Extract in Streptozotocin Induced Diabetic Rats

Bhardwaj

Modi²

2017

Int J Pharm Pharm Sci

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Objective: The main objective of the study was to investigate the effect of ethanol seed extracts of Nelumbo nucifera Gaertn (Nymphaeaceae) as antihyperglycemic, anti-hyperlipidemic and antioxidant activity in streptozotocin-induced diabetic rats.Methods: Diabetes was induced in wistar albino rats by administration of streptozotocin (single intraperitoneal dose of 60 mg/kg B. W). The ethanol extract of N. nucifera seed at a dose of 200 and 400 mg/kg body weight was administrated at a single dose per day to STZ induced diabetic rats for a period of 42 d. The different pharmacological parameters were evaluated. The effect of ethanol seed extract of N. nucifera on insulin, blood glucose, urea, creatinine, HbA1C, serum protein, albumin, globulin, serum enzymes, serum lipid profiles, lipid peroxides (LPO) and other antioxidant enzymes like catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) and reduced glutathione (GSH) were measured in the diabetic rats. Results:In the acute toxicity study ethanol seed extract of Nelumbo nucifera were non-toxic at 2000 mg/kg in rats. The ethanol extract of Nelumbo nucifera seed showed significant reduction in blood glucose (p<0.05), serum enzymes (SGPT, SGOT, ALP) (p<0.05), lipid parameters (TC, TG, VLDL, LDL) (p<0.05) except HDL and significantly increased insulin (p<0.05), HDL (p<0.05), GPx, GSH, SOD and CAT (p<0.05) at the dose of 400 mg/kg when compared with the diabetic-induced control. Conclusion:The present study suggested that the NNSE has significant (p<0.05) antihyperglycemic, antihyperlipidemic and antioxidant activity in STZ induced diabetic rats. These results clearly indicate that Nelumbo nucifera is effective against free radical-mediated diseases, thus replacing the synthetic ones.

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“…The synergy of glycation and oxidation results in formation of advanced glycation end products (AGEs) or glycoxidation products (5), which are able to induce a humoral autoimmune response and, as a consequence, lead to the formation of immune complexes detectable in both serum (6) and atheromatous lesions (7,8). Immune complexes (ICs) isolated from the serum of patients with diabetes contain malondialdehyde-modified and AGE-modified LDL (9), as well as the corresponding antibodies (10), which have been shown to be predominantly of the proinflammatory isotypes IgG1 and IgG3 (9,11).…”

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confidence: 99%

Role of Simvastatin as an Immunomodulator in Type 2 Diabetes

et al. 2004

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OBJECTIVE -To test the hypothesis that simvastatin reduces the levels of circulating immune complexes (ICs) containing modified lipoproteins (mLDLs; mLDL-ICs), which may represent an additional mechanism for the reduced incidence of cardiovascular events in patients treated with simvastatin.RESEARCH DESIGN AND METHODS -A total of 26 patients with type 2 diabetes and triglyceride levels Ͻ400 mg/dl who were not receiving lipid-lowering medications or CYP 3A4 inhibitors were enrolled in the study. After 2 weeks on a lipid-lowering diet and exercise, the patients were started on simvastatin 20 mg/day. The dose of simvastatin was adjusted until the levels of LDL cholesterol were Յ100 mg/dl. Blood was collected at baseline, 3 and 6 months after LDL cholesterol levels reached target, and 3 months after stopping simvastatin to measure advanced glycation end product LDL and oxidized LDL antibodies, mLDL-IC, intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), E-selectin, metalloproteinase-1 (MMP-1), lipid profile, liver function tests, creatinine kinase, glucose, and HbA 1c .RESULTS -Twenty-one patients completed the study. Their HbA 1c remained within 1% of baseline levels. There was a highly significant decrease in mLDL-IC levels after 3 and 6 months of treatment with simvastatin, with a return to near baseline levels after discontinuation.CONCLUSIONS -Simvastatin significantly reduced the concentration of mLDL-IC, probably as a consequence of both a decrease in the formation of mLDL and to a reduction in the titers of mLDL antibodies. This effect is likely to have a beneficial impact in the inflammatory reaction associated with atherosclerosis. Diabetes Care 27:908 -913, 2004D iabetes is associated with increased incidence of macrovascular complications including coronary heart disease (CHD) as well as cerebrovascular and peripheral vascular disease (1,2). The mechanisms behind the accelerated development of atherosclerosis in diabetes and decreased survival after an acute cardiovascular event are poorly understood.Increased levels of modified lipoproteins (mLDLs) have been proposed as significant factors contributing to the accelerated development of macrovascular complications in diabetes (3). The mLDLs emerge, at least in part, as a consequence of chronic hyperglycemia that leads to protein glycation throughout the body. Glycated proteins, including LDL, are more susceptible to oxidation (3,4). The synergy of glycation and oxidation results in formation of advanced glycation end products (AGEs) or glycoxidation products (5), which are able to induce a humoral autoimmune response and, as a consequence, lead to the formation of immune complexes detectable in both serum (6) and atheromatous lesions (7,8). Immune complexes (ICs) isolated from the serum of patients with diabetes contain malondialdehyde-modified and AGE-modified LDL (9), as well as the corresponding antibodies (10), which have been shown to be predominantly of the proinflammatory isotypes IgG1 and IgG3 (9,11).Significantly i...

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Anti-modified LDL antibodies, LDL-containing immune complexes, and susceptibility of LDL to in vitro oxidation in patients with type 2 diabetes.

Cited by 87 publications

References 50 publications

Atherogenesis and the humoral immune response to modified lipoproteins

Atherogenesis and the humoral immune response to modified lipoproteins

Antidiabetic and Antihyperlipidaemic Activity of Nelumbo Nucifera Gaertn Ethanol Seed Extract in Streptozotocin Induced Diabetic Rats

Role of Simvastatin as an Immunomodulator in Type 2 Diabetes

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