Skip to main content
Top
Published in: Cardiovascular Diabetology 1/2015

Open Access 01-12-2015 | Original investigation

Association of elevated apoA-I glycation and reduced HDL-associated paraoxonase1, 3 activity, and their interaction with angiographic severity of coronary artery disease in patients with type 2 diabetes mellitus

Authors: Ying Shen, Feng Hua Ding, Jia Teng Sun, Li Jin Pu, Rui Yan Zhang, Qi Zhang, Qiu Jing Chen, Wei Feng Shen, Lin Lu

Published in: Cardiovascular Diabetology | Issue 1/2015

Login to get access

Abstract

Objective

To investigate whether apolipoprotein A (apoA)-I glycation and paraoxonase (PON) activities are associated with the severity of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM).

Methods

Relative intensity of apoA-I glycation and activities of high-density lipoprotein (HDL)-associated PON1 and PON3 were determined in 205 consecutive T2DM patients with stable angina with (n = 144) or without (n = 61) significant CAD (luminal diameter stenosis ≥ 70 %). The severity of CAD was expressed by number of diseased coronary arteries, extent index, and cumulative coronary stenosis score (CCSS).

Results

The relative intensity of apoA-I glycation was higher but the activities of HDL-associated PON1 and PON3 were lower in diabetic patients with significant CAD than in those without. The relative intensity of apoA-I glycation increased but the activities of HDL-associated PON1 and PON3 decreased stepwise from 1 - to 3 - vessel disease patients (P for trend < 0.001). After adjusting for possible confounding variables, the relative intensity of apoA-I glycation correlated positively, while the activities of HDL-associated PON1 and PON3 negatively, with extent index and CCSS, respectively. At high level of apoA-I glycation (8.70 ~ 12.50 %), low tertile of HDL-associated PON1 (7.03 ~ 38.97U/mL) and PON3 activities (7.11 ~ 22.30U/mL) was associated with a 1.97− and 2.49− fold increase of extent index and 1.73− and 2.68− fold increase of CCSS compared with high tertile of HDL-associated PON1 (57.85 ~ 154.82U/mL) and PON3 activities (39.63 ~ 124.10U/mL), respectively (all P < 0.01).

Conclusions

Elevated apoA-I glycation and decreased activities of HDL-associated PON1 and PON3, and their interaction are associated with the presence and severity of CAD in patients with T2DM.
Appendix
Available only for authorised users
Literature
1.
go back to reference Navab M, Reddy ST, Van Lenten BJ, Fogelman AM. HDL and cardiovascular disease: atherogenic and atheroprotective mechanisms. Nat Rev Cardiol. 2011;8:222–32.CrossRefPubMed Navab M, Reddy ST, Van Lenten BJ, Fogelman AM. HDL and cardiovascular disease: atherogenic and atheroprotective mechanisms. Nat Rev Cardiol. 2011;8:222–32.CrossRefPubMed
5.
go back to reference Ng CJ, Bourguard N, Hama SY, Shih D, Grijalva VR, Navab M, et al. Adenovirus-mediated expression of human paraoxonase 3 protects against the progression of atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2007;27:1368–74.CrossRefPubMed Ng CJ, Bourguard N, Hama SY, Shih D, Grijalva VR, Navab M, et al. Adenovirus-mediated expression of human paraoxonase 3 protects against the progression of atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2007;27:1368–74.CrossRefPubMed
6.
go back to reference Davidson WS, Silva RA, Chantepie S, Lagor WR, Chapman MJ, Kontush A. Proteomic analysis of defined HDL subpopulations reveals particle-specific protein clusters: relevance to anti-oxidative function. Arterioscler Thromb Vasc Biol. 2009;29:870–6.CrossRefPubMedCentralPubMed Davidson WS, Silva RA, Chantepie S, Lagor WR, Chapman MJ, Kontush A. Proteomic analysis of defined HDL subpopulations reveals particle-specific protein clusters: relevance to anti-oxidative function. Arterioscler Thromb Vasc Biol. 2009;29:870–6.CrossRefPubMedCentralPubMed
7.
go back to reference James RW, Deakin SP. The contribution of high density lipoprotein apolipoproteins and derivatives to serum paraoxonase-1 activity and function. Adv Exp Med Biol. 2010;660:173–81.CrossRefPubMed James RW, Deakin SP. The contribution of high density lipoprotein apolipoproteins and derivatives to serum paraoxonase-1 activity and function. Adv Exp Med Biol. 2010;660:173–81.CrossRefPubMed
8.
go back to reference Vakili L, Hama S, Kim JB, Tien D, Safarpoor S, Ly N, et al. The effect of HDL mimetic peptide 4F on PON1. Adv Exp Med Biol. 2010;660:167–72.CrossRefPubMed Vakili L, Hama S, Kim JB, Tien D, Safarpoor S, Ly N, et al. The effect of HDL mimetic peptide 4F on PON1. Adv Exp Med Biol. 2010;660:167–72.CrossRefPubMed
9.
go back to reference Moore RE, Navab M, Millar JS, Zimetti F, Hama S, Rothblat GH, et al. Increased atherosclerosis in mice lacking apolipoprotein A-I attributable to both impaired reverse cholesterol transport and increased inflammation. Circ Res. 2005;97:763–71.CrossRefPubMed Moore RE, Navab M, Millar JS, Zimetti F, Hama S, Rothblat GH, et al. Increased atherosclerosis in mice lacking apolipoprotein A-I attributable to both impaired reverse cholesterol transport and increased inflammation. Circ Res. 2005;97:763–71.CrossRefPubMed
10.
go back to reference Wool GD, Cabana VG, Lukens J, Shaw PX, Binder CJ, Witztum JL, et al. 4F peptide reduces nascent atherosclerosis and induces natural antibody production in apolipoprotein E-null mice. FASEB J. 2011;25:290–300.CrossRefPubMedCentralPubMed Wool GD, Cabana VG, Lukens J, Shaw PX, Binder CJ, Witztum JL, et al. 4F peptide reduces nascent atherosclerosis and induces natural antibody production in apolipoprotein E-null mice. FASEB J. 2011;25:290–300.CrossRefPubMedCentralPubMed
11.
go back to reference Zhang B, Kawachi E, Miura S, Uehara Y, Matsunaga A, Kuroki M, et al. Therapeutic approaches to the regulation of metabolism of high-density lipoprotein. Novel HDL-directed pharmacological intervention and exercise. Circ J. 2013;77:2651–63.CrossRefPubMed Zhang B, Kawachi E, Miura S, Uehara Y, Matsunaga A, Kuroki M, et al. Therapeutic approaches to the regulation of metabolism of high-density lipoprotein. Novel HDL-directed pharmacological intervention and exercise. Circ J. 2013;77:2651–63.CrossRefPubMed
12.
go back to reference Paneni F, Beckman JA, Creager MA, Cosentino F. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical theraphy: part I. Eur Heart J. 2013;34:2436–43.CrossRefPubMedCentralPubMed Paneni F, Beckman JA, Creager MA, Cosentino F. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical theraphy: part I. Eur Heart J. 2013;34:2436–43.CrossRefPubMedCentralPubMed
13.
go back to reference Lambadiari V, Kadoglou NP, Stasinos V, Maratou E, Antoniadis A, Kolokathis F, et al. Serum levels of retinol-binding protein-4 are associated with the presence and severity of coronary artery disease. Cardiovasc Diabetol. 2014;13:121.CrossRefPubMedCentralPubMed Lambadiari V, Kadoglou NP, Stasinos V, Maratou E, Antoniadis A, Kolokathis F, et al. Serum levels of retinol-binding protein-4 are associated with the presence and severity of coronary artery disease. Cardiovasc Diabetol. 2014;13:121.CrossRefPubMedCentralPubMed
14.
go back to reference Li G, Lu WH, Ai R, Yang JH, Chen F, Tang ZZ. The relationship between serum hypoxia-inducible factor 1α and coronary artery calcification in asymptomatic type 2 diabetic patients. Cardiovasc Diabetol. 2014;13:52.CrossRefPubMedCentralPubMed Li G, Lu WH, Ai R, Yang JH, Chen F, Tang ZZ. The relationship between serum hypoxia-inducible factor 1α and coronary artery calcification in asymptomatic type 2 diabetic patients. Cardiovasc Diabetol. 2014;13:52.CrossRefPubMedCentralPubMed
15.
go back to reference Lu L, Pu LJ, Zhang Q, Wang LJ, Kang S, Zhang RY, et al. Increased glycated albumin and decreased esRAGE levels are related to angiographic severity and extent of coronary artery disease in patients with type 2 diabetes. Atherosclerosis. 2009;206:540–5. 20.CrossRefPubMed Lu L, Pu LJ, Zhang Q, Wang LJ, Kang S, Zhang RY, et al. Increased glycated albumin and decreased esRAGE levels are related to angiographic severity and extent of coronary artery disease in patients with type 2 diabetes. Atherosclerosis. 2009;206:540–5. 20.CrossRefPubMed
16.
go back to reference Fukushima Y, Daida H, Morimoto T, Kasai T, Miyauchi K, Yamagishi S, et al. Relationship between advanced glycation end products and plaque progression in patients with acute coronary syndrome: the JAPAN-ACS sub-study. Cardiovasc Diabetol. 2013;12:5.CrossRefPubMedCentralPubMed Fukushima Y, Daida H, Morimoto T, Kasai T, Miyauchi K, Yamagishi S, et al. Relationship between advanced glycation end products and plaque progression in patients with acute coronary syndrome: the JAPAN-ACS sub-study. Cardiovasc Diabetol. 2013;12:5.CrossRefPubMedCentralPubMed
17.
go back to reference Shen Y, Lu L, Ding FH, Sun Z, Zhang RY, Zhang Q, et al. Association of increased serum glycated albumin levels with low coronary collateralization in type 2 diabetic patients with stable angina and chronic total occlusion. Cardiovasc Diabetol. 2013;12:165.CrossRefPubMedCentralPubMed Shen Y, Lu L, Ding FH, Sun Z, Zhang RY, Zhang Q, et al. Association of increased serum glycated albumin levels with low coronary collateralization in type 2 diabetic patients with stable angina and chronic total occlusion. Cardiovasc Diabetol. 2013;12:165.CrossRefPubMedCentralPubMed
18.
go back to reference Hoang A, Murphy AJ, Coughlan MT, Thomas MC, Forbes JM, O’Brien R, et al. Advanced glycation of apolipoprotein A-I impairs its anti-atherogenic properties. Diabetologia. 2007;50:1770–9.CrossRefPubMed Hoang A, Murphy AJ, Coughlan MT, Thomas MC, Forbes JM, O’Brien R, et al. Advanced glycation of apolipoprotein A-I impairs its anti-atherogenic properties. Diabetologia. 2007;50:1770–9.CrossRefPubMed
19.
go back to reference Pu LJ, Lu L, Zhang RY, Du R, Shen Y, Zhang Q, et al. Glycation of apoprotein A-I is associated with coronary artery plaque progression in type 2 diabetic patients. Diabetes Care. 2013;36:1312–20.CrossRefPubMedCentralPubMed Pu LJ, Lu L, Zhang RY, Du R, Shen Y, Zhang Q, et al. Glycation of apoprotein A-I is associated with coronary artery plaque progression in type 2 diabetic patients. Diabetes Care. 2013;36:1312–20.CrossRefPubMedCentralPubMed
20.
go back to reference Nobecourt E, Zeng J, Davies MJ, Brown BE, Yadav S, Barter PJ, et al. Effects of cross-link breakers, glycation inhibitors and insulin sensitisers on HDL function and non-enzymatic glycation of apolipoprotein A-I. Diabetologia. 2008;51:1008–17.CrossRefPubMed Nobecourt E, Zeng J, Davies MJ, Brown BE, Yadav S, Barter PJ, et al. Effects of cross-link breakers, glycation inhibitors and insulin sensitisers on HDL function and non-enzymatic glycation of apolipoprotein A-I. Diabetologia. 2008;51:1008–17.CrossRefPubMed
21.
go back to reference Lebherz C, Sanmiguel J, Wilson JM, Rader DJ. Gene transfer of wild-type apoA-I and apoA-I Milano reduce atherosclerosis to a similar extent. CardiovascDiabetol. 2007;6:15. Lebherz C, Sanmiguel J, Wilson JM, Rader DJ. Gene transfer of wild-type apoA-I and apoA-I Milano reduce atherosclerosis to a similar extent. CardiovascDiabetol. 2007;6:15.
22.
go back to reference Shaw JA, Bobik A, Murphy A, Kanellakis P, Blombery P, Mukhamedova N, et al. Infusion of reconstituted high-density lipoprotein leads to acute changes in human atherosclerotic plaque. Circ Res. 2008;103:1084–91.CrossRefPubMed Shaw JA, Bobik A, Murphy A, Kanellakis P, Blombery P, Mukhamedova N, et al. Infusion of reconstituted high-density lipoprotein leads to acute changes in human atherosclerotic plaque. Circ Res. 2008;103:1084–91.CrossRefPubMed
23.
go back to reference American Diabetes Association. Standards of medical care in diabetes—2012. Diabetes Care. 2012;35 Suppl 1:S11–63. American Diabetes Association. Standards of medical care in diabetes—2012. Diabetes Care. 2012;35 Suppl 1:S11–63.
24.
go back to reference Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, IZZO JL, et al. Seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. 2003;42:1206–52.CrossRefPubMed Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, IZZO JL, et al. Seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. 2003;42:1206–52.CrossRefPubMed
25.
go back to reference Grundy SM, Cleeman JI, Merz CN, Brewer Jr HB, Clark LT, Hunninghake DB, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110:227–39.CrossRefPubMed Grundy SM, Cleeman JI, Merz CN, Brewer Jr HB, Clark LT, Hunninghake DB, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110:227–39.CrossRefPubMed
26.
go back to reference Mark WJ, Azen SP, Dunn M, Hodis HN. A comparison of quantitative computerized and human panel coronary endpoint measures: Implications for the design of angiographic trials. Control Clin Trials. 1997;18:168–79.CrossRef Mark WJ, Azen SP, Dunn M, Hodis HN. A comparison of quantitative computerized and human panel coronary endpoint measures: Implications for the design of angiographic trials. Control Clin Trials. 1997;18:168–79.CrossRef
27.
go back to reference Solymoss BC, Bourassa MG, Campeau L, Sniderman A, Marcil M, Lesperance J, et al. Effect of increasing metabolic syndrome score on atherosclerotic risk profile and coronary artery disease angiographic severity. Am J Cardiol. 2004;93:159–64.CrossRefPubMed Solymoss BC, Bourassa MG, Campeau L, Sniderman A, Marcil M, Lesperance J, et al. Effect of increasing metabolic syndrome score on atherosclerotic risk profile and coronary artery disease angiographic severity. Am J Cardiol. 2004;93:159–64.CrossRefPubMed
28.
go back to reference Ren S, Shen GX. Impact of antioxidants and HDL on glycated LDL-induced generation of fibrinolytic regulators from vascular endothelial cells. Arterioscler Thromb Vasc Biol. 2000;20:1688–93.CrossRefPubMed Ren S, Shen GX. Impact of antioxidants and HDL on glycated LDL-induced generation of fibrinolytic regulators from vascular endothelial cells. Arterioscler Thromb Vasc Biol. 2000;20:1688–93.CrossRefPubMed
29.
go back to reference Aviram M, Rosenblat M. Paraoxonases (PON1, PON2, PON3) analysis in vitro and in vivo in relation to cardiovascular diseases. Methods MolBiol. 2008;477:259–76. Aviram M, Rosenblat M. Paraoxonases (PON1, PON2, PON3) analysis in vitro and in vivo in relation to cardiovascular diseases. Methods MolBiol. 2008;477:259–76.
30.
go back to reference Weers PM, Patel AB, Wan LC, Guigard E, Kay CM, Hafiane A, et al. Novel N-terminal mutation of human apolipoprotein A-I reduces self-association and impairs LCAT activation. J Lipid Res. 2011;52(1):35–44.CrossRefPubMedCentralPubMed Weers PM, Patel AB, Wan LC, Guigard E, Kay CM, Hafiane A, et al. Novel N-terminal mutation of human apolipoprotein A-I reduces self-association and impairs LCAT activation. J Lipid Res. 2011;52(1):35–44.CrossRefPubMedCentralPubMed
31.
go back to reference Jang W, Jeoung NH, Cho KH. Modified apolipoprotein (apo) A-I by artificial sweetener causes severe premature cellular senescence and atherosclerosis with impairment of functional and structural properties of apoA-I in lipid-free and lipid-bound state. Mol Cells. 2011;31:461–70.CrossRefPubMedCentralPubMed Jang W, Jeoung NH, Cho KH. Modified apolipoprotein (apo) A-I by artificial sweetener causes severe premature cellular senescence and atherosclerosis with impairment of functional and structural properties of apoA-I in lipid-free and lipid-bound state. Mol Cells. 2011;31:461–70.CrossRefPubMedCentralPubMed
32.
go back to reference Shao B, Pennathur S, Heinecke JW. Myeloperoxidase targets apolipoprotein A-I, the major high density lipoprotein protein, for site-specific oxidation in human atherosclerotic lesions. J Biol Chem. 2012;287(9):6375–86.35.CrossRefPubMedCentralPubMed Shao B, Pennathur S, Heinecke JW. Myeloperoxidase targets apolipoprotein A-I, the major high density lipoprotein protein, for site-specific oxidation in human atherosclerotic lesions. J Biol Chem. 2012;287(9):6375–86.35.CrossRefPubMedCentralPubMed
33.
go back to reference Murakami H, Tanabe J, Tamasawa N, Matsumura K, Yamashita M, Murakami H, et al. Reduction of paraoxonase-1 activity may contribute the qualitative impairment of HDL particles in patients with type 2 diabetes. Diabetes Res Clin Pract. 2013;99:30–8.CrossRefPubMed Murakami H, Tanabe J, Tamasawa N, Matsumura K, Yamashita M, Murakami H, et al. Reduction of paraoxonase-1 activity may contribute the qualitative impairment of HDL particles in patients with type 2 diabetes. Diabetes Res Clin Pract. 2013;99:30–8.CrossRefPubMed
34.
go back to reference Fekih O, Triki S, Hellara J, Neffati F, Chouchane S, Neji Gueddiche M, Fadhel Naijar M. Is paraoxonase 1 a marker of cardiovascular risk in youth with type 1 diabetes? (Study about 109 cases) Presse Med. 2015 Mar 10. doi:10.1016/j.lpm.2014.10.020. [Epub ahead of print] Fekih O, Triki S, Hellara J, Neffati F, Chouchane S, Neji Gueddiche M, Fadhel Naijar M. Is paraoxonase 1 a marker of cardiovascular risk in youth with type 1 diabetes? (Study about 109 cases) Presse Med. 2015 Mar 10. doi:10.1016/j.lpm.2014.10.020. [Epub ahead of print]
35.
go back to reference Alegria-Torres JA, Garcia-Dominquez ML, Cruz M, Aradillas-Garcia C. Q192R polymorphism of paraoxonase 1 gene associated with insulin resistance in Mexican children. Arch Med Res. 2015;46:78–83.CrossRefPubMed Alegria-Torres JA, Garcia-Dominquez ML, Cruz M, Aradillas-Garcia C. Q192R polymorphism of paraoxonase 1 gene associated with insulin resistance in Mexican children. Arch Med Res. 2015;46:78–83.CrossRefPubMed
Metadata
Title
Association of elevated apoA-I glycation and reduced HDL-associated paraoxonase1, 3 activity, and their interaction with angiographic severity of coronary artery disease in patients with type 2 diabetes mellitus
Authors
Ying Shen
Feng Hua Ding
Jia Teng Sun
Li Jin Pu
Rui Yan Zhang
Qi Zhang
Qiu Jing Chen
Wei Feng Shen
Lin Lu
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2015
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-015-0221-4

Other articles of this Issue 1/2015

Cardiovascular Diabetology 1/2015 Go to the issue
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

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.