The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis

Masako Tabuchi, Katsumi Inoue, Hitomi Kataoka, Kazuko Kobayashi, Misako Teramoto, Koji Takasugi, Kenichi Shikata, Masahiro Yamamura, Kenji Ando, Keiichiro Nishida, Junko Kasahara, Noriaki Kume, Luis R. Lopez, Kazuaki Mitsudo, Masakiyo Nobuyoshi, Tatsuji Yasuda, Toru Kita, Hirofumi Makino, Eiji Matsuura

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

C-reactive protein (CRP) is one of the strongest independent predictors of cardiovascular disease. We have previously reported that oxidized LDL (oxLDL) interacts with β2-glycoprotein I (β2GPI), implicating oxLDL/β2GPI complexes as putative autoantigens in autoimmune-mediated atherosclerotic vascular disease. In this study, we investigated the interaction of CRP with oxLDL/β2GPI complexes and its association with atherosclerosis in patients with diabetes mellitus (DM). CRP/oxLDL/β2GPI complexes were predominantly found in sera of DM patients with atherosclerosis. In contrast, noncomplexed CRP isoforms were present in sera of patients with acute/chronic inflammation, i.e., various pyrogenic diseases, rheumatoid arthritis (RA), and DM. Immunohistochemistry staining colocalized CRP and β2GPI together with oxLDL in carotid artery plaques but not in synovial tissue from RA patients, strongly suggesting that complex formation occurs during the development of atherosclerosis. Serum levels of CRP correlated with soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and oxLDL/β2GPI complexes correlated with total cholesterol and hemoglobin A1c. Thus, the generation of CRP/oxLDL/β2GPI complexes seems to be associated with arterial inflammation, hyperglycemia, and hypercholesterolemia. CRP/oxLDL/β2GPI complexes can be distinguished from pyrogenic noncomplexed CRP isoforms and may represent a more specific and predictive marker for atherosclerosis.

Original languageEnglish
Pages (from-to)768-781
Number of pages14
JournalJournal of Lipid Research
Volume48
Issue number4
DOIs
Publication statusPublished - Apr 2007

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Metabolites
C-Reactive Protein
Atherosclerosis
Glycoproteins
LDL Lipoproteins
Medical problems
Diabetes Mellitus
Rheumatoid Arthritis
Protein Isoforms
Serum
oxidized low density lipoprotein
Arteritis
Vascular Cell Adhesion Molecule-1
Carotid Stenosis
Autoantigens
Intercellular Adhesion Molecule-1
Hypercholesterolemia
Vascular Diseases
Hyperglycemia
Hemoglobins

Keywords

  • β2-glycoprotein I
  • Diabetes mellitus
  • Oxidized LDL
  • Oxidized LDL/β2-glycoprotein I complexes

ASJC Scopus subject areas

  • Endocrinology

Cite this

The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis. / Tabuchi, Masako; Inoue, Katsumi; Kataoka, Hitomi; Kobayashi, Kazuko; Teramoto, Misako; Takasugi, Koji; Shikata, Kenichi; Yamamura, Masahiro; Ando, Kenji; Nishida, Keiichiro; Kasahara, Junko; Kume, Noriaki; Lopez, Luis R.; Mitsudo, Kazuaki; Nobuyoshi, Masakiyo; Yasuda, Tatsuji; Kita, Toru; Makino, Hirofumi; Matsuura, Eiji.

In: Journal of Lipid Research, Vol. 48, No. 4, 04.2007, p. 768-781.

Research output: Contribution to journalArticle

Tabuchi, M, Inoue, K, Kataoka, H, Kobayashi, K, Teramoto, M, Takasugi, K, Shikata, K, Yamamura, M, Ando, K, Nishida, K, Kasahara, J, Kume, N, Lopez, LR, Mitsudo, K, Nobuyoshi, M, Yasuda, T, Kita, T, Makino, H & Matsuura, E 2007, 'The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis', Journal of Lipid Research, vol. 48, no. 4, pp. 768-781. https://doi.org/10.1194/jlr.M600414-JLR200
Tabuchi, Masako ; Inoue, Katsumi ; Kataoka, Hitomi ; Kobayashi, Kazuko ; Teramoto, Misako ; Takasugi, Koji ; Shikata, Kenichi ; Yamamura, Masahiro ; Ando, Kenji ; Nishida, Keiichiro ; Kasahara, Junko ; Kume, Noriaki ; Lopez, Luis R. ; Mitsudo, Kazuaki ; Nobuyoshi, Masakiyo ; Yasuda, Tatsuji ; Kita, Toru ; Makino, Hirofumi ; Matsuura, Eiji. / The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis. In: Journal of Lipid Research. 2007 ; Vol. 48, No. 4. pp. 768-781.
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abstract = "C-reactive protein (CRP) is one of the strongest independent predictors of cardiovascular disease. We have previously reported that oxidized LDL (oxLDL) interacts with β2-glycoprotein I (β2GPI), implicating oxLDL/β2GPI complexes as putative autoantigens in autoimmune-mediated atherosclerotic vascular disease. In this study, we investigated the interaction of CRP with oxLDL/β2GPI complexes and its association with atherosclerosis in patients with diabetes mellitus (DM). CRP/oxLDL/β2GPI complexes were predominantly found in sera of DM patients with atherosclerosis. In contrast, noncomplexed CRP isoforms were present in sera of patients with acute/chronic inflammation, i.e., various pyrogenic diseases, rheumatoid arthritis (RA), and DM. Immunohistochemistry staining colocalized CRP and β2GPI together with oxLDL in carotid artery plaques but not in synovial tissue from RA patients, strongly suggesting that complex formation occurs during the development of atherosclerosis. Serum levels of CRP correlated with soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and oxLDL/β2GPI complexes correlated with total cholesterol and hemoglobin A1c. Thus, the generation of CRP/oxLDL/β2GPI complexes seems to be associated with arterial inflammation, hyperglycemia, and hypercholesterolemia. CRP/oxLDL/β2GPI complexes can be distinguished from pyrogenic noncomplexed CRP isoforms and may represent a more specific and predictive marker for atherosclerosis.",
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AU - Tabuchi, Masako

AU - Inoue, Katsumi

AU - Kataoka, Hitomi

AU - Kobayashi, Kazuko

AU - Teramoto, Misako

AU - Takasugi, Koji

AU - Shikata, Kenichi

AU - Yamamura, Masahiro

AU - Ando, Kenji

AU - Nishida, Keiichiro

AU - Kasahara, Junko

AU - Kume, Noriaki

AU - Lopez, Luis R.

AU - Mitsudo, Kazuaki

AU - Nobuyoshi, Masakiyo

AU - Yasuda, Tatsuji

AU - Kita, Toru

AU - Makino, Hirofumi

AU - Matsuura, Eiji

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N2 - C-reactive protein (CRP) is one of the strongest independent predictors of cardiovascular disease. We have previously reported that oxidized LDL (oxLDL) interacts with β2-glycoprotein I (β2GPI), implicating oxLDL/β2GPI complexes as putative autoantigens in autoimmune-mediated atherosclerotic vascular disease. In this study, we investigated the interaction of CRP with oxLDL/β2GPI complexes and its association with atherosclerosis in patients with diabetes mellitus (DM). CRP/oxLDL/β2GPI complexes were predominantly found in sera of DM patients with atherosclerosis. In contrast, noncomplexed CRP isoforms were present in sera of patients with acute/chronic inflammation, i.e., various pyrogenic diseases, rheumatoid arthritis (RA), and DM. Immunohistochemistry staining colocalized CRP and β2GPI together with oxLDL in carotid artery plaques but not in synovial tissue from RA patients, strongly suggesting that complex formation occurs during the development of atherosclerosis. Serum levels of CRP correlated with soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and oxLDL/β2GPI complexes correlated with total cholesterol and hemoglobin A1c. Thus, the generation of CRP/oxLDL/β2GPI complexes seems to be associated with arterial inflammation, hyperglycemia, and hypercholesterolemia. CRP/oxLDL/β2GPI complexes can be distinguished from pyrogenic noncomplexed CRP isoforms and may represent a more specific and predictive marker for atherosclerosis.

AB - C-reactive protein (CRP) is one of the strongest independent predictors of cardiovascular disease. We have previously reported that oxidized LDL (oxLDL) interacts with β2-glycoprotein I (β2GPI), implicating oxLDL/β2GPI complexes as putative autoantigens in autoimmune-mediated atherosclerotic vascular disease. In this study, we investigated the interaction of CRP with oxLDL/β2GPI complexes and its association with atherosclerosis in patients with diabetes mellitus (DM). CRP/oxLDL/β2GPI complexes were predominantly found in sera of DM patients with atherosclerosis. In contrast, noncomplexed CRP isoforms were present in sera of patients with acute/chronic inflammation, i.e., various pyrogenic diseases, rheumatoid arthritis (RA), and DM. Immunohistochemistry staining colocalized CRP and β2GPI together with oxLDL in carotid artery plaques but not in synovial tissue from RA patients, strongly suggesting that complex formation occurs during the development of atherosclerosis. Serum levels of CRP correlated with soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and oxLDL/β2GPI complexes correlated with total cholesterol and hemoglobin A1c. Thus, the generation of CRP/oxLDL/β2GPI complexes seems to be associated with arterial inflammation, hyperglycemia, and hypercholesterolemia. CRP/oxLDL/β2GPI complexes can be distinguished from pyrogenic noncomplexed CRP isoforms and may represent a more specific and predictive marker for atherosclerosis.

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