Elevated AGE-modified ApoB in sera of euglycemic, normolipidemic patients with atherosclerosis

Relationship to tissue AGEs

Alan William Stitt, Cijiang He, Steven Friedman, Larry A. Scher, Peter Rossi, Larry Ong, Hank Founds, Yong Ming Li, Richard Bucala, Helen Vlassara

Research output: Contribution to journalArticle

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Abstract

Background: Advanced glycation endproducts (AGEs) are implicated in the pathogenesis of atherosclerotic vascular disease of diabetic and hondiabetic etiology. Recent research suggests that advanced glycation of ApoB contributes to the development of hyperlipidemia. AGE-specific receptors, expressed on vascular endothelium and mononuclear cells, may be involved in both the clearance of and the inflammatory responses to AGEs. The aim of this study was to examine whether there is a relationship between serum AGE-ApoB and AGEs in arterial tissue of older normolipidemic nondiabetic patients with occlusive atherosclerotic disease, compared with age-matched and younger asymptomatic persons. Materials and Methods: Serum AGE-ApoB was measured by ELISA in 21 cardiac bypass patients. Furthermore, an AGE-specific monoclonal antibody, and polyclonal antibodies against anti-AGE-receptor (anti-AGE-R) 1 and 2 were used to explore the localization and distribution of AGEs and AGE- R immunoreactivity (IR) in arterial segments excised from these patients. Results: Serum AGE-ApoB levels were significantly elevated in the asymptomatic, older population, compared with those in young healthy persons (259 ± 24 versus 180 ± 21 AGE U/mg of ApoB, p < 0.01). Higher AGE-ApoB levels were observed in those patients with atherosclerosis (329 ±23 versus 259 ± 24 AGE U/mg ApoB, p < 0.05). Comparisons of tissue AGE-collagen with serum AGE-ApoB levels showed a significant correlation (r = 0.707, p < 0.01). In early lesions, AGE-IR occurred mostly extracellularly. In fatty streaks and dense, cellular atheromatous lesions, AGE-IR was visible within lipid- containing smooth muscle cells and macrophages, while in late-stage, acellular plaques, AGE-IR occurred mostly extracellularly. AGE-R1 and -R2 were observed on vascular endothelial and smooth-muscle cells and on infiltrating mononuclear cells in the early-stage lesions, whereas in dense, late-stage plaques, they colocalized mostly with lipid-laden macrophages. On tissue sections; scoring of AGE-immunolluorescence correlated with tissue AGE and plasma AGE-ApoB. Conclusions: (I) The correlation between arterial tissue AGEs and circulating AGE-ApoB suggests a causal link between AGE modification of lipoproteins and atherosclerosis. AGE-specific receptors may contribute to this process. (2) Serum AGE-ApoB may serve to predict atherosclerosis in asymptomatic patients.

Original languageEnglish (US)
Pages (from-to)617-627
Number of pages11
JournalMolecular Medicine
Volume3
Issue number9
StatePublished - 1997

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Apolipoproteins B
Atherosclerosis
Serum
Smooth Muscle Myocytes
Macrophages
Lipids
Diabetic Angiopathies
Vascular Endothelium
Hyperlipidemias
Vascular Smooth Muscle
Lipoproteins
Anti-Idiotypic Antibodies
Collagen
Enzyme-Linked Immunosorbent Assay
Monoclonal Antibodies

ASJC Scopus subject areas

  • Genetics

Cite this

Elevated AGE-modified ApoB in sera of euglycemic, normolipidemic patients with atherosclerosis : Relationship to tissue AGEs. / Stitt, Alan William; He, Cijiang; Friedman, Steven; Scher, Larry A.; Rossi, Peter; Ong, Larry; Founds, Hank; Li, Yong Ming; Bucala, Richard; Vlassara, Helen.

In: Molecular Medicine, Vol. 3, No. 9, 1997, p. 617-627.

Research output: Contribution to journalArticle

Stitt, AW, He, C, Friedman, S, Scher, LA, Rossi, P, Ong, L, Founds, H, Li, YM, Bucala, R & Vlassara, H 1997, 'Elevated AGE-modified ApoB in sera of euglycemic, normolipidemic patients with atherosclerosis: Relationship to tissue AGEs', Molecular Medicine, vol. 3, no. 9, pp. 617-627.
Stitt, Alan William ; He, Cijiang ; Friedman, Steven ; Scher, Larry A. ; Rossi, Peter ; Ong, Larry ; Founds, Hank ; Li, Yong Ming ; Bucala, Richard ; Vlassara, Helen. / Elevated AGE-modified ApoB in sera of euglycemic, normolipidemic patients with atherosclerosis : Relationship to tissue AGEs. In: Molecular Medicine. 1997 ; Vol. 3, No. 9. pp. 617-627.
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title = "Elevated AGE-modified ApoB in sera of euglycemic, normolipidemic patients with atherosclerosis: Relationship to tissue AGEs",
abstract = "Background: Advanced glycation endproducts (AGEs) are implicated in the pathogenesis of atherosclerotic vascular disease of diabetic and hondiabetic etiology. Recent research suggests that advanced glycation of ApoB contributes to the development of hyperlipidemia. AGE-specific receptors, expressed on vascular endothelium and mononuclear cells, may be involved in both the clearance of and the inflammatory responses to AGEs. The aim of this study was to examine whether there is a relationship between serum AGE-ApoB and AGEs in arterial tissue of older normolipidemic nondiabetic patients with occlusive atherosclerotic disease, compared with age-matched and younger asymptomatic persons. Materials and Methods: Serum AGE-ApoB was measured by ELISA in 21 cardiac bypass patients. Furthermore, an AGE-specific monoclonal antibody, and polyclonal antibodies against anti-AGE-receptor (anti-AGE-R) 1 and 2 were used to explore the localization and distribution of AGEs and AGE- R immunoreactivity (IR) in arterial segments excised from these patients. Results: Serum AGE-ApoB levels were significantly elevated in the asymptomatic, older population, compared with those in young healthy persons (259 ± 24 versus 180 ± 21 AGE U/mg of ApoB, p < 0.01). Higher AGE-ApoB levels were observed in those patients with atherosclerosis (329 ±23 versus 259 ± 24 AGE U/mg ApoB, p < 0.05). Comparisons of tissue AGE-collagen with serum AGE-ApoB levels showed a significant correlation (r = 0.707, p < 0.01). In early lesions, AGE-IR occurred mostly extracellularly. In fatty streaks and dense, cellular atheromatous lesions, AGE-IR was visible within lipid- containing smooth muscle cells and macrophages, while in late-stage, acellular plaques, AGE-IR occurred mostly extracellularly. AGE-R1 and -R2 were observed on vascular endothelial and smooth-muscle cells and on infiltrating mononuclear cells in the early-stage lesions, whereas in dense, late-stage plaques, they colocalized mostly with lipid-laden macrophages. On tissue sections; scoring of AGE-immunolluorescence correlated with tissue AGE and plasma AGE-ApoB. Conclusions: (I) The correlation between arterial tissue AGEs and circulating AGE-ApoB suggests a causal link between AGE modification of lipoproteins and atherosclerosis. AGE-specific receptors may contribute to this process. (2) Serum AGE-ApoB may serve to predict atherosclerosis in asymptomatic patients.",
author = "Stitt, {Alan William} and Cijiang He and Steven Friedman and Scher, {Larry A.} and Peter Rossi and Larry Ong and Hank Founds and Li, {Yong Ming} and Richard Bucala and Helen Vlassara",
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T1 - Elevated AGE-modified ApoB in sera of euglycemic, normolipidemic patients with atherosclerosis

T2 - Relationship to tissue AGEs

AU - Stitt, Alan William

AU - He, Cijiang

AU - Friedman, Steven

AU - Scher, Larry A.

AU - Rossi, Peter

AU - Ong, Larry

AU - Founds, Hank

AU - Li, Yong Ming

AU - Bucala, Richard

AU - Vlassara, Helen

PY - 1997

Y1 - 1997

N2 - Background: Advanced glycation endproducts (AGEs) are implicated in the pathogenesis of atherosclerotic vascular disease of diabetic and hondiabetic etiology. Recent research suggests that advanced glycation of ApoB contributes to the development of hyperlipidemia. AGE-specific receptors, expressed on vascular endothelium and mononuclear cells, may be involved in both the clearance of and the inflammatory responses to AGEs. The aim of this study was to examine whether there is a relationship between serum AGE-ApoB and AGEs in arterial tissue of older normolipidemic nondiabetic patients with occlusive atherosclerotic disease, compared with age-matched and younger asymptomatic persons. Materials and Methods: Serum AGE-ApoB was measured by ELISA in 21 cardiac bypass patients. Furthermore, an AGE-specific monoclonal antibody, and polyclonal antibodies against anti-AGE-receptor (anti-AGE-R) 1 and 2 were used to explore the localization and distribution of AGEs and AGE- R immunoreactivity (IR) in arterial segments excised from these patients. Results: Serum AGE-ApoB levels were significantly elevated in the asymptomatic, older population, compared with those in young healthy persons (259 ± 24 versus 180 ± 21 AGE U/mg of ApoB, p < 0.01). Higher AGE-ApoB levels were observed in those patients with atherosclerosis (329 ±23 versus 259 ± 24 AGE U/mg ApoB, p < 0.05). Comparisons of tissue AGE-collagen with serum AGE-ApoB levels showed a significant correlation (r = 0.707, p < 0.01). In early lesions, AGE-IR occurred mostly extracellularly. In fatty streaks and dense, cellular atheromatous lesions, AGE-IR was visible within lipid- containing smooth muscle cells and macrophages, while in late-stage, acellular plaques, AGE-IR occurred mostly extracellularly. AGE-R1 and -R2 were observed on vascular endothelial and smooth-muscle cells and on infiltrating mononuclear cells in the early-stage lesions, whereas in dense, late-stage plaques, they colocalized mostly with lipid-laden macrophages. On tissue sections; scoring of AGE-immunolluorescence correlated with tissue AGE and plasma AGE-ApoB. Conclusions: (I) The correlation between arterial tissue AGEs and circulating AGE-ApoB suggests a causal link between AGE modification of lipoproteins and atherosclerosis. AGE-specific receptors may contribute to this process. (2) Serum AGE-ApoB may serve to predict atherosclerosis in asymptomatic patients.

AB - Background: Advanced glycation endproducts (AGEs) are implicated in the pathogenesis of atherosclerotic vascular disease of diabetic and hondiabetic etiology. Recent research suggests that advanced glycation of ApoB contributes to the development of hyperlipidemia. AGE-specific receptors, expressed on vascular endothelium and mononuclear cells, may be involved in both the clearance of and the inflammatory responses to AGEs. The aim of this study was to examine whether there is a relationship between serum AGE-ApoB and AGEs in arterial tissue of older normolipidemic nondiabetic patients with occlusive atherosclerotic disease, compared with age-matched and younger asymptomatic persons. Materials and Methods: Serum AGE-ApoB was measured by ELISA in 21 cardiac bypass patients. Furthermore, an AGE-specific monoclonal antibody, and polyclonal antibodies against anti-AGE-receptor (anti-AGE-R) 1 and 2 were used to explore the localization and distribution of AGEs and AGE- R immunoreactivity (IR) in arterial segments excised from these patients. Results: Serum AGE-ApoB levels were significantly elevated in the asymptomatic, older population, compared with those in young healthy persons (259 ± 24 versus 180 ± 21 AGE U/mg of ApoB, p < 0.01). Higher AGE-ApoB levels were observed in those patients with atherosclerosis (329 ±23 versus 259 ± 24 AGE U/mg ApoB, p < 0.05). Comparisons of tissue AGE-collagen with serum AGE-ApoB levels showed a significant correlation (r = 0.707, p < 0.01). In early lesions, AGE-IR occurred mostly extracellularly. In fatty streaks and dense, cellular atheromatous lesions, AGE-IR was visible within lipid- containing smooth muscle cells and macrophages, while in late-stage, acellular plaques, AGE-IR occurred mostly extracellularly. AGE-R1 and -R2 were observed on vascular endothelial and smooth-muscle cells and on infiltrating mononuclear cells in the early-stage lesions, whereas in dense, late-stage plaques, they colocalized mostly with lipid-laden macrophages. On tissue sections; scoring of AGE-immunolluorescence correlated with tissue AGE and plasma AGE-ApoB. Conclusions: (I) The correlation between arterial tissue AGEs and circulating AGE-ApoB suggests a causal link between AGE modification of lipoproteins and atherosclerosis. AGE-specific receptors may contribute to this process. (2) Serum AGE-ApoB may serve to predict atherosclerosis in asymptomatic patients.

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