Determination of serum 7-ketocholesterol concentrations and their relationships with coronary multiple risks in diabetes mellitus

Endo, Kei; Oyama, Tomokazu; Saiki, Atsuhito; Ban, Noriko; Ohira, Masahiro; Koide, Nobukiyo; Murano, Takeyoshi; Watanabe, Hitoshi; Nishii, Manabu; Miura, Masaya; Sekine, Kyoichi; Miyashita, Yoh; Shirai, Kohji

doi:10.1016/j.diabres.2007.10.023

Cited by 40 publications

(29 citation statements)

References 27 publications

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“…In line with such a hypothesis, serum concentrations of 7-ketocholesterol (7κ-C) and 7β-hydroxycholesterol (7β OH-C), the most abundant OS-derived oxysterols that are carried on oxLDL [115], have been consistently associated with the occurrence of T2D and correlated with coronary multiple risks [103,116]. Moreover, oxLDL and 7κ-C were also reported to impair (pre) adipocyte differentiation and induce IR in mature adipocytes [104,117,118].…”

Section: Oxysterolsmentioning

confidence: 93%

“…Among lipid peroxidation products, the nonenzymatic oxysterols and the reactive aldehyde 4-HNE have received the most attention because increasing data indicate their mechanistic implication in the pathophysiology of obesity-linked metabolic diseases [95,96,[99][100][101][102][103][104][105][106].…”

Section: Lipid Peroxidation At the Crossroads Of Adipose Dysfunctionmentioning

confidence: 99%

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Lipokines and oxysterols: Novel adipose-derived lipid hormones linking adipose dysfunction and insulin resistance

Murdolo¹,

Bartolini

Tortoioli³

et al. 2013

Free Radical Biology and Medicine

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Section: Oxysterolsmentioning

confidence: 93%

Section: Lipid Peroxidation At the Crossroads Of Adipose Dysfunctionmentioning

confidence: 99%

Lipokines and oxysterols: Novel adipose-derived lipid hormones linking adipose dysfunction and insulin resistance

Murdolo¹,

Bartolini

Tortoioli³

et al. 2013

Free Radical Biology and Medicine

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“…Although information is limited, evidence to date suggests that circulating concentrations of oxysterols and oxLDLs are increased in pregnant women with diabetes, obesity, pre-eclampsia and IUGR (Zwirska-Korczala et al, 2001;Bodzek et al, 2002;Uzun et al, 2005;Qiu et al, 2006;Kim et al, 2007;Endo et al, 2008;Leduc et al, 2011;Makedou et al, 2011), all conditions in which oxidative stress has been described. With respect to the actual levels documented, several clinical studies have reported normal plasma levels of oxysterols in the mid to high nanogram/milliliter range (Dzeletovic et al, 1995;Iuliano et al, 2003;Endo et al, 2008). However, levels of oxysterols generated de novo in sites of oxidative stress, such as atherosclerotic lesions, are known to increase by 90 -200-fold depending on the severity of the lesion (Garcia-Cruset et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…However, several reports indicate an association between elevated circulating oxysterol levels and metabolic disorders including diabetes and obesity (Zwirska-Korczala et al, 2001;Bodzek et al, 2002;Endo et al, 2008). Additionally, oxLDL levels are also elevated with pregnancy (Makedou et al, 2011) and higher concentrations are reported in women with pre-eclampsia (Uzun et al, 2005;Qiu et al, 2006;Kim et al, 2007) and in the cord blood of neonates with intrauterine growth restriction (Leduc et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Oxysterols exert proinflammatory effects in placental trophoblasts via TLR4-dependent, cholesterol-sensitive activation of NF- B

Aye

Waddell

Mark

et al. 2012

Molecular Human Reproduction

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Oxidized cholesterol metabolites (oxysterols) promote inflammation in a variety of cell types and are thought to be involved in a number of disease pathologies. Oxysterol concentrations are increased in pregnancy, together with systemic oxidative stress and inflammation. We tested the hypothesis that oxysterols 25-hydroxycholesterol (25-OHC) and 7-ketocholesterol (7-ketoC) promote placental trophoblast inflammation, and determined the mechanisms involved. Treatment of primary trophoblasts in culture with 25-OHC and 7-ketoC increased the production of proinflammatory cytokines (interleukin-6, macrophage inflammatory protein-1b and tumour necrosis factor-a) in a concentration-dependent fashion. Inhibition of TLR4 activation using selective inhibitors of TLR4 complex formation (OxPAPC) or signalling transmission (CLI095) prevented lipopolysaccharide (LPS)-and oxysterol-induced inflammatory cytokine production. Pretreatment of trophoblasts with selective inhibitors of I-kB kinase activity (parthenolide and TPCA-1) reduced oxysterol-and LPS-stimulated inflammatory responses, consistent with the involvement of the nuclear factor kappa B (NF-kB) pathway downstream of TLR4 signalling. Both oxysterols also increased the phosphorylation and nuclear localization of NF-kB subunit p65/RelA. Oxysterols are also known to activate liver X receptors (LXRs) which can inhibit inflammatory signalling, either directly or indirectly via membrane cholesterol reduction. Treatment with the LXR agonist, T0901317, exerted significant anti-inflammatory effects, reducing LPS-and oxysteroldriven cytokine production. Treatment with methyl-b-cyclodextrin to deplete membrane microdomain cholesterol and thereby disrupt TLR4 signalling, similarly abrogated their effects. Together, these findings indicate that although oxysterols likely activate both pro-and anti-inflammatory pathways in the placenta, the predominant effect is the promotion of placental inflammation via TLR4-dependent activation of NF-kB.

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“…Furthermore, a high intake of oxysterol is reported to deteriorate atherosclerosis 25) . Our previous data demonstrated that the serum oxysterol concentration in type 2 diabetic patients, who are reported to have high absorption of cholesterol 5) , was significantly higher than in healthy subjects 26) . Ezetimibe was reported to inhibit oxysterol absorption 27) .…”

Section: Discussionmentioning

confidence: 99%

Effect of Ezetimibe Monotherapy on Lipid Metabolism and Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Type 2 Diabetic Patients

Miyashita

Endo

Saiki

et al. 2010

JAT

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Aim: High cholesterol absorption in the small intestine has been proposed to be a risk factor of atherosclerosis. In this study, we evaluated the effect of ezetimibe monotherapy on arterial stiffness in type 2 diabetic patients. Methods: Forty type 2 diabetes mellitus patients with high serum low-density lipoprotein cholesterol (LDL-C) were enrolled and treated with ezetimibe 10 mg/day for 6 months. HbA1c, serum lipids, remnant-like particle-cholesterol (RLP-C), serum lipoprotein lipase mass (LPL mass) and the cardioankle vascular index (CAVI) were measured before and after ezetimibe treatment. Results: After 6 months of ezetimibe treatment, significant decreases in LDL-C, RLP-C and CAVI were observed. In the group that achieved the LDL-C goal of 120 mg/dL after 6 months of ezetimibe treatment, the pretreatment CAVI was markedly high, and CAVI decreased significantly after ezetimibe treatment. Conclusions: In type 2 diabetic patients, ezetimibe monotherapy may have the potential to ameliorate arterial stiffness in addition to lowering LDL-C and RLP-C.

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Determination of serum 7-ketocholesterol concentrations and their relationships with coronary multiple risks in diabetes mellitus

Cited by 40 publications

References 27 publications

Lipokines and oxysterols: Novel adipose-derived lipid hormones linking adipose dysfunction and insulin resistance

Lipokines and oxysterols: Novel adipose-derived lipid hormones linking adipose dysfunction and insulin resistance

Oxysterols exert proinflammatory effects in placental trophoblasts via TLR4-dependent, cholesterol-sensitive activation of NF- B

Effect of Ezetimibe Monotherapy on Lipid Metabolism and Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Type 2 Diabetic Patients

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