Oxidized low-density lipoprotein levels circulating in plasma and deposited in the tissues: Comparison between Helicobacter pylori-associated gastritis and acute myocardial infarction

Kayo, Soichiro; Ohsawa, Masahiko; Ehara, Shoichi; Naruko, Takahiko; Hai, Eishu; Yoshimi, Noriko; Shirai, Nobuyuki; Tsukamoto, Yoshiaki; Itabe, Hiroyuki; Higuchi, Kazuhide; Ueda, Makiko

doi:10.1016/j.ahj.2004.05.042

Cited by 36 publications

(43 citation statements)

References 39 publications

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“…[8][9][10] We recently developed a novel specific antibody against oxPC, 17,18 and using this antibody, we demonstrated the localization of oxLDL in macrophages accumulated in human atherosclerotic lesions. [9][10][11] In the current study, we investigated the localization of oxPC in normal and NASH/NAFLD liver tissues using the same antibody. As a result, we found oxPC predominantly in steatotic hepatocytes and macrophages/Kupffer cells, and was more abundant in NASH/NAFLD livers than in normal control livers.…”

Section: Discussionmentioning

confidence: 99%

“…8 Oxidatively modified lowdensity lipoprotein (oxidized low-density lipoprotein; oxLDL) is thought to be an atherogenic factor due to its localization in macrophage-derived foam cells accumulated in human atherosclerotic lesions. [9][10][11] OxLDL has cytotoxicity and macrophage chemoattractivity, which may be important in the genesis of the inflammatory process associated with atherosclerotic plaques. [12][13][14] Cellular uptake of oxLDL is mediated by the binding of oxidized phosphatidylcholine (oxPC) molecules, the principal oxidized phospholipid present in oxLDL, to scavenger receptors.…”

mentioning

confidence: 99%

“…17,18 Using this antibody, we have investigated the influence of oxidative stress on various diseases. [9][10][11]19 The aim of this study is to clarify the degree of oxidative stress in NASH/NAFLD by means of immunohistochemical examination using this antibody.…”

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confidence: 99%

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Localization of oxidized phosphatidylcholine in nonalcoholic fatty liver disease: Impact on disease progression

Ikura¹,

Ohsawa²,

Suekane³

et al. 2006

Hepatology

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127

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Nonalcoholic steatohepatitis/nonalcoholic fatty liver disease is considered to be a hepatic manifestation of various metabolic disorders. However, its precise pathogenic mechanism is obscure. Oxidative stress and consequent lipid peroxidation seem to play a pivotal role in disease progression. In this study, we analyzed the localization of oxidized phosphatidylcholine (oxPC), a lipid peroxide that serves as a ligand for scavenger receptors, in livers of patients with this steatotic disorder. Specimens of nonalcoholic fatty liver disease (15 autopsy livers with simple steatosis and 32 biopsy livers with steatohepatitis) were examined via immunohistochemistry and immunoelectron microscopy using a specific antibody against oxPC. In addition, scavenger receptor expression, hepatocyte apoptosis, iron deposition, and inflammatory cell infiltration in the diseased livers were also assessed. Oxidized phosphatidylcholine was mainly localized to steatotic hepatocytes and some macrophages/Kupffer cells. A few degenerative or apoptotic hepatocytes were also positive for oxPC. Immunoelectron microscopy showed oxPC localized to cytoplasmic/intracytoplasmic membranes including lipid droplets. Steatotic livers showed enhanced expression of scavenger receptors. The number of oxPC cells was correlated with disease severity and the number of myeloperoxidasepositive neutrophils, but not with the degree of iron deposition. In conclusion, distinct localization of oxPC in liver tissues suggest that neutrophil myeloperoxidase-derived oxidative stress may be crucial in the formation of oxPC and the progression of steatotic liver disease. (HEPATOLOGY 2006;43:506-514.)

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Localization of oxidized phosphatidylcholine in nonalcoholic fatty liver disease: Impact on disease progression

Ikura¹,

Ohsawa²,

Suekane³

et al. 2006

Hepatology

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127

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“…DLH3 is specific for ox-LDL, because it recognizes oxidized phosphatidylcholine (ox-PC) molecules and does not react with either native, acetylated, malondialdehyde-treated, or glycated LDL 18) . With this sensitive method, we demonstrated a significant association between plasma ox-LDL levels and the severity of coronary syndromes 12,14) . Recently, we also reported that persistence of an elevated level of plasma ox-LDL after an AMI is a strong independent predictor of stent restenosis at 6-month follow-up 17) .…”

mentioning

confidence: 90%

“…Previous in vitro studies have shown that oxidized low density lipoprotein (ox-LDL) is a key factor in the pathogenesis of these inflammatory processes 8) . Recently, the detection of ox-LDL in circulating plasma has been reported [9][10][11][12][13][14][15][16][17] . We developed a new method to determine the levels of ox-LDL in human circulating plasma, using an anti-ox-LDL monoclonal antibody, DLH3 11) .…”

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confidence: 99%

Small Coronary Calcium Deposits and Elevated Plasma Levels of Oxidized Low Density Lipoprotein are Characteristic of Acute Myocardial Infarction

Ehara

Naruko

Shirai

et al. 2008

JAT

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Aim:Predictions of the onset of acute myocardial infarction (AMI) in high risk individuals are of great clinical importance. Among various risk factors, elevated levels of oxidized low density lipoprotein (ox-LDL) in plasma have been shown to reflect unstable coronary plaques. Coronary calcification is a common finding in the elderly, however, its clinical implications as a risk factor for plaque rupture are controversial. This study was designed to investigate the clinical implications of plasma ox-LDL levels and coronary calcification detected by electron-beam computed tomography (EBCT), by comparing patients with AMI with those with stable angina pectoris (SAP). Methods: We measured plasma ox-LDL levels in AMI (n 34) and SAP (n 49) patients. In addition, a coronary calcium score was quantified with the Agatston system. The total coronary calcium score (TCS) was defined as the sum of the scores for each lesion. Results: TCS and total calcium area were significantly smaller in patients with AMI than in those with SAP. On the other hand, plasma ox-LDL levels were significantly higher in AMI patients than in SAP patients (p 0.0005). Conclusion: These results suggest that a combined assessment of coronary calcium and plasma ox-LDL levels may be useful for screening patients with unstable coronary plaques. J Atheroscler

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Specific immunization strategies against oxidized low-density lipoprotein: A novel way to reduce nonalcoholic steatohepatitis in mice

et al. 2012

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Background Non-alcoholic steatohepatitis (NASH) is characterized by hepatic lipid accumulation combined with inflammation, which can ultimately progress into cirrhosis. Recently, we demonstrated that deletion of scavenger receptors (SR) CD36 and SR-A in haematopoietic cells reduced hepatic inflammation. In addition to uptake of modified lipoproteins, CD36 and SR-A are also involved in other functions that can activate the inflammatory response. Therefore, the actual trigger for SR activation during NASH is unclear. Here, we hypothesized that hepatic inflammation is triggered by recognition of oxidized LDL (oxLDL) by Kupffer cells (KCs). Methods To inhibit recognition of oxLDL by KCs, Ldlr−/− mice were immunized with heat-inactivated pneumococci, which were shown to induce the production of anti-oxLDL IgM antibodies, due to molecular mimicry with oxLDL. The mice received a high fat cholesterol (HFC) diet during the last 3 weeks to induce NASH. Results Immunization with pneumococci increased anti-oxLDL IgM levels and led to a reduction in hepatic inflammation, as shown by reduced macrophage, neutrophil and T-cell infiltration, and reduced gene expression of Tnf, Il-6, Il-1β, Mcp1 and fibrosis related genes. In immunized mice, KCs were smaller and showed less cholesterol crystals compared to non-immunized mice. Conclusion Antibodies to oxLDL play an important role in the pathogenesis of NASH. Therefore, the potential of PC-based vaccination strategies as a novel tool for the prevention and therapy of NASH should be tested in future.

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Oxidized low-density lipoprotein levels circulating in plasma and deposited in the tissues: Comparison between Helicobacter pylori-associated gastritis and acute myocardial infarction

Cited by 36 publications

References 39 publications

Localization of oxidized phosphatidylcholine in nonalcoholic fatty liver disease: Impact on disease progression

Localization of oxidized phosphatidylcholine in nonalcoholic fatty liver disease: Impact on disease progression

Small Coronary Calcium Deposits and Elevated Plasma Levels of Oxidized Low Density Lipoprotein are Characteristic of Acute Myocardial Infarction

Specific immunization strategies against oxidized low-density lipoprotein: A novel way to reduce nonalcoholic steatohepatitis in mice

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