Upregulation of Monocyte Tissue Factor Activity Is Significantly Associated With Low-Grade Chronic Inflammation and Insulin Resistance in Patients With Metabolic Syndrome

Nakagomi, Akihiro; Sasaki, Mihoko; Ishikawa, Youhei; Morikawa, Masako; Shibui, Toshiyuki; Kusama, Yoshiki; Atarashi, Hirotsugu; Mizuno, Kyoichi

doi:10.1253/circj.cj-09-0835

Cited by 29 publications

(20 citation statements)

References 26 publications

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“…In the present study, the TNF-and MCP-1 levels were reduced by 36%, and 28%, respectively, in the patients treated with pitavastatin, compared to only 21% and 11%, respectively, in those receiving independently associated with the mean CIMT 23) . In addition, we reported that patients with carotid atherosclerosis show significantly higher hsCRP levels and have lower overall HDL cholesterol levels in comparison to those without carotid atherosclerosis, thus indicating that inflammation and insulin resistance play significant roles in the pathogenesis and progression of carotid atherosclerosis in patients with MS 24) .…”

Section: Safetycontrasting

confidence: 46%

Differential Effects of Atorvastatin and Pitavastatin on Inflammation, Insulin Resistance, and the Carotid Intima-Media Thickness in Patients with Dyslipidemia

Nakagomi

Shibui²,

Kohashi

et al. 2015

J Atheroscler Thromb

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Section: Safetycontrasting

confidence: 46%

Differential Effects of Atorvastatin and Pitavastatin on Inflammation, Insulin Resistance, and the Carotid Intima-Media Thickness in Patients with Dyslipidemia

Nakagomi

Shibui²,

Kohashi

et al. 2015

J Atheroscler Thromb

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“…In patients with MetS with diabetes, Fortuño et al (22) showed increased NADPH oxidase activity and increased plasma levels of both nitrotyrosine and oxidized LDL levels, clearly supporting increased oxidative stress. Also, Nakagomi et al (23) showed increased tissue factor procoagulant activity in patients with MetS, which correlated with increased endotoxin levels, CRP, and HOMA. However, it is unclear from their reports if they excluded patients with diabetes and smokers because in their second report, which showed a correlation with carotid intima-media thickness (24), 67% of the patients were diabetic and 63% were smokers.…”

Section: Discussionmentioning

confidence: 96%

Increased Toll-Like Receptor Activity in Patients With Metabolic Syndrome

et al. 2012

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OBJECTIVEThe metabolic syndrome (MetS) is highly prevalent and confers an increased risk for diabetes and cardiovascular disease (CVD). While MetS is a proinflammatory state, there is a paucity of data on cellular inflammation in MetS. Toll-like receptors (TLRs) are classical pattern recognition receptors of the innate immune response.RESEARCH DESIGN AND METHODSThe aim of this study was to examine monocyte TLR2 and TLR4 in MetS patients without diabetes or CVD and control subjects since both of the receptors have been implicated in atherosclerosis and insulin resistance. Fasting blood was obtained for TLR expression and activity.RESULTSCirculating levels of high-sensitivity C-reactive protein, interleukin (IL)-1β, IL-6, IL-8, and soluble tumor necrosis factor receptor 1 (sTNFR1) were significantly increased in MetS versus control subjects following adjustment for waist circumference. There was a significant increase in both TLR2 and TLR4 surface expression and mRNA on monocytes after adjustment for waist circumference. In addition to increased nuclear factor-κB nuclear binding, there was significantly increased release of IL-1β, IL-6, and IL-8 in MetS versus control subjects following priming of the monocytes with lipopolysaccharides. While both plasma free fatty acids and endotoxin were increased in MetS, they correlated significantly with TLR4 only.CONCLUSIONSIn conclusion, we make the novel observation that both TLR2 and TLR4 expression and activity are increased in the monocytes of patients with MetS and could contribute to increased risk for diabetes and CVD.

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“…This finding is consistent with evidence that monocytes play a key role in metabolic homeostasis, and produce inflammatory mediators in response to cues that modulate metabolism (Bhargava and Lee, 2012). Subjects with metabolic syndrome have significantly higher monocytic tissue factor pro-coagulant activity, and up-regulation of monocyte tissue factor is associated with insulin resistance, higher hsCRP, and carotid intima-media thickness, a significant predictor of cardiovascular events (Nakagomi et al, 2010; Nakagomi et al, 2011). Subjects with the metabolic syndrome also have up-regulation of monocytic CD40/CD40 ligand expression (Natal et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Total and differential white blood cell counts, high-sensitivity C-reactive protein, and the metabolic syndrome in non-affective psychoses

Miller¹,

Mellor²,

Buckley³

2013

Brain, Behavior, and Immunity

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The metabolic syndrome is highly prevalent in patients with schizophrenia, and is associated with a state of chronic, low-grade inflammation. Schizophrenia is also associated with increased inflammation, including aberrant blood levels of pro-inflammatory cytokines and high-sensitivity C-reactive protein (hsCRP). The purpose of this study is to investigate the relationship between total and differential white blood cell (WBC) counts, hsCRP, and the metabolic syndrome in patients with schizophrenia and related non-affective psychoses. 59 inpatients and outpatients age 18–70 with non-affective psychotic disorders and 22 controls participated in this cross-sectional study. Subjects had a fasting blood draw between 8 and 9 am for glucose, lipids, total and differential WBC counts, and hsCRP. Vital signs and anthropometric measures were obtained. Patients with non-affective psychosis and the metabolic syndrome had significantly higher total WBC counts, monocytes, and hsCRP levels than patients without the metabolic syndrome (p≤0.04 for each). In binary logistic regression analyses, after controlling for potential confounding effects of age, race, sex, age at first hospitalization for psychosis, parental history of diabetes, smoking, and psychotropic medications, total WBC count, monocytes, and hsCRP were significant predictors of metabolic syndrome in patients (p≤0.04 for each). hsCRP was also a significant predictor of increased waist circumference and triglycerides in patients (p≤0.05 for each). Our findings suggest that measurement of total and differential WBC counts and hsCRP blood levels may be germane to the clinical care of patients with schizophrenia and related disorders, and support an association between inflammation and metabolic disturbance in these patients.

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Upregulation of Monocyte Tissue Factor Activity Is Significantly Associated With Low-Grade Chronic Inflammation and Insulin Resistance in Patients With Metabolic Syndrome

Cited by 29 publications

References 26 publications

Differential Effects of Atorvastatin and Pitavastatin on Inflammation, Insulin Resistance, and the Carotid Intima-Media Thickness in Patients with Dyslipidemia

Differential Effects of Atorvastatin and Pitavastatin on Inflammation, Insulin Resistance, and the Carotid Intima-Media Thickness in Patients with Dyslipidemia

Increased Toll-Like Receptor Activity in Patients With Metabolic Syndrome

Total and differential white blood cell counts, high-sensitivity C-reactive protein, and the metabolic syndrome in non-affective psychoses

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