The oxidative modification hypothesis of atherosclerosis: The comparison of atherogenic effects on oxidized LDL and remnant lipoproteins in plasma

Nakajima, Katsuyuki; Nakano, Takamitsu; Tanaka, Akira

doi:10.1016/j.cca.2005.12.013

Cited by 160 publications

(131 citation statements)

References 135 publications

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“…25 In addition, it has always been puzzling that LDL particles need to be oxidized before they can be taken up by macrophages, whereas triglyceride-rich lipoproteins or remnants can be taken up by macrophages without oxidation. 26 These observations from cell culture studies may therefore help explain why elevated remnant cholesterol in humans is causally associated with low-grade inflammation but elevated LDL cholesterol is not. Taken together, this suggests that elevated LDL cholesterol causes atherosclerosis without a major inflammatory component, whereas an inflammatory component of atherosclerosis is driven by elevated nonfasting remnant cholesterol.…”

Section: Discussionmentioning

confidence: 99%

Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, Whereas Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease Without Inflammation

et al. 2013

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Background-Elevated nonfasting remnant cholesterol and low-density lipoprotein (LDL) cholesterol are causally associated with ischemic heart disease (IHD), but whether elevated nonfasting remnant cholesterol and LDL cholesterol both cause low-grade inflammation is currently unknown. Methods and Results-We studied 60 608 individuals from the Copenhagen General Population Study, the Copenhagen City Heart Study, and the Copenhagen Ischemic Heart Disease study, of whom 10 668 had IHD diagnosed between 1977 and 2011. We genotyped for variants affecting levels of nonfasting remnant cholesterol, LDL cholesterol, C-reactive protein by CRP alleles, and C-reactive protein by IL6R alleles. Using a multidirectional mendelian randomization design, we investigated possible causal associations between the lipoproteins and C-reactive protein and between the lipoproteins and IHD. A 1-mmol/L(39 mg/dL) higher level of nonfasting remnant cholesterol was associated observationally with a 37% (95% confidence interval, 35-39) higher C-reactive protein level and causally with a 28% (95% confidence interval, 10-48) higher level. For LDL cholesterol, a 1-mmol/L (39-mg/dL) higher level was associated observationally with a 7% (95% confidence interval, 6-7) higher C-reactive protein level, but we found no causal association. Likewise, higher levels of C-reactive protein did not associate causally with elevated nonfasting remnant cholesterol or LDL cholesterol. Finally, the causal risk ratio for IHD for a 1-mmol/L (39-mg/dL) higher level was 3.3 (95% confidence interval, 2.1-5.2) for nonfasting remnant cholesterol and 1.8 (95% confidence interval, 1.5-2.2) for LDL cholesterol. The causal associations for remnant cholesterol were present even in those without diabetes mellitus and obesity. Conclusions-Elevated nonfasting remnant cholesterol is causally associated with low-grade inflammation and with IHD, whereas elevated LDL cholesterol is associated causally with IHD without inflammation. (Circulation. 2013;128:1298-1309.)

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Section: Discussionmentioning

confidence: 99%

Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, Whereas Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease Without Inflammation

et al. 2013

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“…The oxidation of LDL has been widely studied in order to understand better the role of LDL oxidation in vivo in pathological situation, such as atherogenesis (1). For this purpose, in vitro models have been developed including the oxidation of LDL by copper (14).…”

Section: Resultsmentioning

confidence: 99%

“…The susceptibility of low density lipoprotein (LDL) to oxidation is believed to be an important factor in the process responsible for foam cell formation and atherosclerosis (1). The common evaluation methods of LDL susceptibility to oxidation in vitro are based on LDL oxidation induced either by transition metals (usually copper) or by organic free radical generators (2)(3).…”

Section: Introductionmentioning

confidence: 99%

Kinetic study of low density lipoprotein oxidation by copper

Ghaffari

Ghiasvand

2010

Indian J Clin Biochem

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“…Ox-LDL has been implicated as a key initiator in a number of plaque promoting processes [106] receptor activation and activation of the intrinsic mitochondrial pathway involving Bcl-2, cytochrome c and caspase-3. The targeting of multiple pathways by ox-LDL underlines the importance of what has been proven in epidemiological studies to be a key risk factor clinically for cardiovascular disease.…”

Section: Macrovascular Complications-cardiovascular Disease and Macromentioning

confidence: 99%

Diabetes mellitus and apoptosis: inflammatory cells

et al. 2009

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Since the early observation that similarities between thyroiditis and insulitis existed, the important role played by inflammation in the development of diabetes has been appreciated. More recently, experiments have shown that inflammation also plays a prominent role in the development of target organ damage arising as complications, with both elements of the innate and the adaptive immune system being involved, and that cytokines contributing to local tissue damage may arise from both infiltrating and resident cells. This review will discuss the experimental evidence that shows that inflammatory cellmediated apoptosis contributes to target organ damage, from beta cell destruction to both micro-and macro-vascular disease complications, and also how alterations in leukocyte turnover affects immune function.

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The oxidative modification hypothesis of atherosclerosis: The comparison of atherogenic effects on oxidized LDL and remnant lipoproteins in plasma

Cited by 160 publications

References 135 publications

Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, Whereas Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease Without Inflammation

Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, Whereas Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease Without Inflammation

Kinetic study of low density lipoprotein oxidation by copper

Diabetes mellitus and apoptosis: inflammatory cells

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