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Neck and shoulder stiffness is a typical subjective symptom in developed countries. This stiffness is caused by factors such as muscle tension and poor blood flow, leading to reduce work efficiency and diminish QOL. NKCP

Purpose The blood levels of Adiponectin, anti-inflammatory and anti-arteriosclerotic adipocytokine, decrease due to smoking and obesity. Cigarette smokers are generally known to gain weight after smoking cessation (SC). Nevertheless, precise changes in serum adiponectin levels after SC and specific effects of abdominal obesity on those changes remain unknown. The objective of this study was to elucidate the changes in serum adiponectin levels after SC and the effects of abdominal obesity on those changes. Methods In 86 patients (56 males and 30 females) who had successfully quit smoking, serum adiponectin levels were measured using an enzyme-linked immunosorbent assay at baseline and 1 year after beginning SC. Results Body mass index and waist circumference (WC) were significantly increased 1 year after beginning SC. Adiponectin levels, however, did not change after SC. Using the median ΔWC (+2.8%) as the cutoff point, patients were then divided into two groups. The percent change in adiponectin levels from baseline to 1 year was significantly greater in the ΔWC < median group (−1.1%) than in the ΔWC ≥ median group (+8.1%) (p = 0.011). Conclusions Despite weight gain and increased abdominal obesity, serum adiponectin levels did not decrease after SC. Therefore, the beneficial effect of SC may eliminate the adverse effects of subsequent weight gain. Conversely, patients with less abdominal obesity had increased adiponectin levels 1 year after SC. Therefore, in such patients, the beneficial effect of SC on adiponectin levels is apparent.

BACKGROUND: Heart failure (HF) is a heterogeneous syndrome, but the effect of the type and severity of HF on the incidence of stroke or systemic embolism (SE) in atrial fibrillation (AF) patients is unclear.Methods and Results:The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. Follow-up data were available for 3,749 patients. We defined pre-existing HF as having one of the following: prior hospitalization for HF, presence of HF symptoms (NYHA ≥2), or reduced ejection fraction (CONCLUSIONS: The effect of HF on the incidence of stroke/SE may depend on the stage or severity of HF in patients with AF. The incidence of stroke/SE was markedly increased in the 30 days after admission for HF, but compensated 'stable' HF did not appear to confer an independent risk.

Signals activated by increased hemodynamic overload to the heart finally reach the nuclei of cardiac myocytes and induce maladaptive hypertrophy in them. Nuclear acetylation, which is controlled by histone deacetylases and the intrinsic histone acetyltransferase p300, is a critical event in this process. We previously found that a natural p300 HAT inhibitor, curcumin, can inhibit cardiomyocyte hypertrophy and the development of heart failure in vivo. However, curcumin is insoluble in water, and its bioavailability is low. Therefore, a more efficient system for heart failure therapy is desirable for actual clinical practice. To overcome this limitation, we recently synthesized a curcumin analog, GO-Y030, which possesses stronger anti-cancer activity than curcumin. However, the effect of GO-Y030 on heart failure is still unclear. The purpose of this study was to determine whether GO-Y030 inhibits p300-HAT activity and can be used as a therapeutic agent for heart failure.

Maladaptive hypertrophy is being recognized as a critical event during the development of heart failure. In a previous study, we demonstrated that a natural compound, curcumin, prevented cardiomyocyte hypertrophy and the development of heart failure in two different model animals.[1–4] Recently, we screened a natural compound library and found that nobiletin, a poly-methoxy flavonoid derived from Citrus unshu, repressed phenylephrine (PE)-induced hypertrophic responses in cardiomyocytes and prevented the deterioration of systolic function and LV pathological hypertrophy in animals with myocardial infarction and pressure-overload. Thus, nobiletin is expected as an attractive pharmacological agent for the treatment of heart failure. However, the target molecule of nobiletin in cardiomyocytes is still unclear. To solve this problem, we attempted to identify novel nobiletin-binding proteins by a proteomics approach and investigate its functional mechanism in mice.

It is reported that 3 months of professional smoking cessation treatment achieves an initial smoking cessation rate of 80 %. However, a 1 year cessation rate decreases to approximately 50 %. The most common causes of relapse are weight gain, stress, and nicotine withdrawal symptoms. Relapse prevention is important in smoking cessation treatment. The aim of the present study was to investigate the differences between those who continued smoking cessation (group A) and those who resumed (group B) at 1 year after smoking cessation.

A recent multicenter registry study of venous thromboembolism (VTE) patients in Japan demonstrated a high prevalence of inferior vena cava (IVC) filter placement. However, data regarding indications, applications, and outcomes of IVC filters in Japanese patients are quite limited. This study was an observational, single-center, retrospective cohort study of all consecutive patients with acute VTE treated between March 2006 and February 2014. Data extracted included patient demographics, indications, applications, and complications of IVC filters, as well as VTE recurrence and death. A total of 257 consecutive patients were analyzed. Seventy-eight patients (30 %) received IVC filters. The proportions of IVC filter placement were 26 % for deep-vein thrombosis (DVT) alone, 10 % for pulmonary embolism (PE) alone, and 46 % for both DVT and PE. There was no significant difference in patient demographics between the IVC filter group and no-IVC filter group. Stated indications for filter placement were 24 cases (30 %) of DVT in intrapelvic veins, 16 cases (20 %) of DVT in proximal veins, and 11 cases (14 %) of contraindication to anticoagulant therapy. In the IVC filter group, cases of class I indication (guidelines: JCS 75:1258-1281, 2009) numbered only 6 (8 %). Many of the retrievable IVC filters were not removed and placed permanently and the retrieval rate was 42 %. We found complications of IVC filters in 8 cases (10 %). IVC filter placement was significantly associated with a better survival rate and a higher incidence of DVT recurrence during a mean observation period of 541 days. Our research suggests the frequent use of IVC filters for VTE treatment, combined with a low retrieval rate. Most of the stated indications of IVC filter placement for VTE in Japanese patients were cases of DVT in intrapelvic veins or proximal veins, not cases of contraindication to anticoagulant therapy.

Curcumin is a major constituent of the spice turmeric and has various biological activities, including anticancer, antioxidant, and anti-inflammatory properties, as well as alcohol detoxification. However, because of its poor absorption efficiency, it is difficult for orally administered curcumin to reach blood levels sufficient to exert its bioactivities. To overcome this problem, several curcumin preparations with a drug-delivery system (DDS) have been developed to increase the bioavailability of curcumin after oral administration, and tested as functional foods and potential medical agents in humans. We have also produced capsules containing Theracurmin, curcumin dispersed with colloidal submicron-particles. To evaluate the absorption efficiency of three types of DDS curcumin, we performed a double-blind, 3-way crossover study. We compared plasma curcumin levels after the administration of Theracurmin and 2 other capsule types of curcumin with DDS, BCM-95 (micronized curcumin with turmeric essential oils) and Meriva (curcumin-phospholipid). Nine healthy subjects (male/female=5/4, age: 24-32 y old) were administered these 3 preparations of DDS curcumin, at commonly used dosages. Six capsules of Theracurmin, 1 capsule of BCM-95, and 2 capsules of Meriva contain 182.4 ± 1.0, 279.3 ± 10.7, and 152.5 ± 20.3 mg of curcumin, respectively. The maximal plasma curcumin concentration (0-24 h) of Theracurmin was 10.7 to 5.6 times higher than those of BCM-95 and Meriva, respectively. Moreover, the area under the blood concentration-time curve at 0-24 h was found to be 11.0- and 4.6-fold higher with Theracurmin than BCM-95 and Meriva, respectively. These data indicate that Theracurmin exhibits a much higher absorption efficiency than other curcumin DDS preparations.

Statins, 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors, are potential drugs for chronic heart failure treatment in clinical studies. However, there may be differences in the effects on heart failure between lipophilic and hydrophilic statins. In this study, we investigated whether hydrophilic rosuvastatin (RSV) and lipophilic pitavastatin (PTV) exert different effects on the left ventricular diastolic function. Subjects were hypercholesterolemia patients with left ventricular diastolic dysfunction. This was an open-label, randomized, parallel, comparative, prospective study. The subjects received treatment with RSV or PTV for 24 weeks, and their low density lipoprotein (LDL)-cholesterol levels were controlled by these statins according to the guideline. The primary endpoint was defined as the change in left ventricle (LV) diastolic function (E/E') estimated by echocardiography, and the secondary endpoint was the plasma B-type natriuretic peptide (BNP) level. No serious adverse effects were observed during the entire study period in any patient, nor were there any significant differences in changes in the body mass index, blood pressure, or heart rate. Statin treatment did not significantly alter the primary endpoint, E/E'. The change ratio of BNP was not significantly different between PTV and RSV groups. However, BNP was significantly increased in the RSV (p=0.030) but not the PTV (p>0.999) group. This study revealed that although neither RSV nor PTV improved LV diastolic dysfunction, BNP, a biomarker of LV wall stress, was increased in the RSV but not the PTV group. Observation for a longer period is necessary to clarify the different effects of these statins on LV diastolic dysfunction. (UMIN-ID: UMIN000003571).

The aim of this study is to determine which indicator of chronic kidney disease most closely correlates with 10-year Framingham coronary heart disease (CHD) risk among serum creatinine, serum cystatin C (S-CysC), urine albumin-creatinine ratio (UACR), estimated creatinine-based GFRs (eGFRcre), and estimated CysC-based GFRs (eGFRcys) in patients with obesity and diabetes. Serum creatinine, S-CysC, UACR, and cardio-ankle vascular index (CAVI) were examined in 468 outpatients with obesity and type 2 diabetes, free of severe renal dysfunction or previous history of cardiovascular disease, as a cross-sectional survey using baseline data from the multi-centered Japan Diabetes and Obesity Study. S-CysC and eGFRcys had significantly stronger correlations with the 10-year Framingham CHD risk than serum creatinine, eGFRcre, and UACR (creatinine, ρ = 0.318; S-CysC, ρ = 0.497; UACR, ρ = 0.174; eGFRcre, ρ = -0.291; eGFRcys, ρ = -0.521; P < 0.01 by Fisher's z-test). S-CysC and eGFRcys had significantly stronger correlations with CAVI than serum creatinine, eGFRcre, and UACR (creatinine, ρ = 0.198; S-CysC, ρ = 0.383; UACR, ρ = 0.183; eGFRcre, ρ = -0.302; eGFRcys, ρ = -0.444; P < 0.05 by Fisher's z-test). The receiver operating characteristic curves to distinguish the high-risk patients for CHD revealed significantly larger areas under the curve of S-CysC and eGFRcys than those of serum creatinine, UACR, and eGFRcre (serum creatinine, 0.64; S-CysC, 0.75; UACR, 0.56; eGFRcre, 0.63; eGFRcys, 0.76; P < 0.01). The data suggested that eGFRcys can be more predictive of the 10-year CHD risk than eGFRcre in Japanese patients with obesity and diabetes.

Objective The expression level of monocyte chemoattractant protein-1 (MCP-1) is increased in atherosclerotic regions, inducing monocyte migration to the blood vessel wall. Although the serum MCP-1 concentration is higher in patients with than without cardiovascular disease, the precise correlations between the serum MCP-1 concentration and factors associated with smoking and atherosclerosis are unknown. Methods The serum MCP-1 concentration was measured using an enzyme-linked immunosorbent assay in 207 consecutive smokers who visited our smoking cessation clinic. Results Sex-adjusted analysis of smokers revealed that the MCP-1 concentration was positively correlated with age ( β = 0.311), smoking duration ( β = 0.342), systolic blood pressure ( β = 0.225), and diastolic blood pressure ( β = 0.137) but not with the body mass index. Multivariate regression analysis showed that smoking duration and systolic blood pressure were independent determinants of the MCP-1 concentration. Conclusions The MCP-1 concentration was positively correlated with blood pressure among smokers. Long-term smokers with high blood pressure may be more susceptible to plaque rupture at atherosclerotic lesion sites.

The clinical characteristics and outcomes of asymptomatic patients with paroxysmal or persistent/permanent atrial fibrillation (AF) are largely unknown.The Fushimi AF Registry is a community-based prospective survey of patients with AF who visited the participating medical institutions in Fushimi-ku, Japan. We investigated the clinical characteristics and outcomes of asymptomatic vs symptomatic patients in the paroxysmal AF (PAF; n = 1,837) and persistent/permanent (sustained atrial fibrillation [SAF]; n = 1,912) subgroups.In the PAF group, asymptomatic patients were older (asymptomatic vs symptomatic group, 74.1 vs 71.1 years of age; P .01), more often male (62.1% vs 55.6%; P .01), and had a higher CHAAsymptomatic clinical status is associated with older age, male sex, more co-morbidities with a higher stroke risk profile, and a higher incidence of all-cause death in patients with PAF; these characteristics and outcomes were not seen in the SAF group.UMIN Clinical Trials Registry; No.: UMIN000005834; URL: www.umin.ac.jp/ctr/index.htm.

Vessel wall inflammation promotes the destabilization of atherosclerotic plaques. The lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) expressed by vascular cells and monocytes. LOX index is calculated by multiplying LOX-1 ligand containing apolipoprotein B level with the soluble LOX-1. A high LOX index reflects an increased risk for stroke and myocardial infarction. However, the change in LOX index after smoking cessation and the relationship between smoking-related variables and LOX index are unknown. Relation of the clinical parameters to the LOX index was examined on 180 subjects (135 males and 45 females) at the first visit to our outpatient clinic for smoking cessation. The impact of smoking cessation on the LOX index was also determined in the 94 subjects (62 males and 32 females) who successfully stopped smoking. Sex-adjusted regression analysis and multivariate analysis identified three independent determinants of the LOX index, namely, low-density lipoprotein-cholesterol (LDL-C; β = 0.311, p

Background: Vessel walls Inflammation is involved in the destabilization of atherosclerotic plaques. Lectin-like low-density lipoprotein (LDL) receptor-1 (LOX-1) is an oxidized LDL receptor expressed in vascular cells and monocytes. The LOX index is calculated by multiplying the concentration of LOX-1 ligand containing apolipoprotein B with the concentration of soluble LOX-1. A high LOX index reflects an increased risk for stroke and myocardial infarction. Fortunately, the cardiovascular risk decreases within 2 years after smoking cessation. However, no study has investigated the potential of the LOX index as a cardiovascular risk marker in smokers, and the relationship between the LOX index and smoking cessation. Purpose: The present study investigated the change of cardiovascular risk marker, LOX index, after smoking cessation and the relationship between smoking-related factors and LOX index. In addition, the present study investigated the impact of smoking cessation on the LOX index. Methods: Relation of the clinical parameters to the LOX index was examined on 207 subjects (155 males and 52 females) at the first visit to our outpatient clinic for smoking cessation. All anti-smoking treatments were conducted according to the Standard Procedures for Anti-Smoking Treatment (originally issued in March 2006 by the Japanese Circulation Society, Japan Lung Cancer Society, and Japanese Cancer Association). The patients were treated with transdermal nicotine patches or the oral administration of varenicline. Among patients who attended our smoking cessation clinic, 94 subjects (62 males and 32 females) successfully quit smoking. We determined their LOX index at baseline on their first visit and repeated it 3 months after beginning smoking cessation to assess the impact of smoking cessation on the LOX index. Results: Sex-adjusted regression analysis and multivariate analysis identified three independent determinants of the LOX index, namely low-density lipoprotein-cholesterol (LDL-C; β = 0.273, p = 0.002), high-sensitivity C-reactive protein (β = 0.324, p < 0.001), and expired carbon monoxide concentration reflecting the amount of smoking (β = 0.225, p = 0.008). Body mass index (BMI) significantly increased 3 months after the onset of smoking cessation (p < 0.001). However, the LOX index significantly decreased from baseline to 3 months (from 3.31 to 2.57; p < 0.001), regardless of the rate of increase in BMI post-cessation. Conclusions: The LOX index is closely associated with hsCRP, a common inflammatory marker, suggesting that LOX-1 is involved in cardiovascular events by inducing vessel wall inflammation. Our results also suggest that the LOX index is useful for evaluating the effects of smoking cessation intervention on cardiovascular risk reduction. In addition, smoking cessation may induce a decrease in this cardiovascular risk marker, independently of weight gain.

Background: Adipocytokines are produced and secreted by the adipose tissue and are strongly associated with obesity. Among these cytokines, adiponectin prevents arteriosclerosis. In obesity, the serum adiponectin levels decrease whereas leptin levels increase. However, the association between these two adipocytokines and abdominal obesity after smoking cessation is unknown. Purpose: The present study investigated time-dependent changes after smoking cessation of two adipocytokines, adiponectin and leptin, as well as the changes of body mass index and waist circumstance (WC). Methods: All anti-smoking treatments were conducted according to the Standard Procedures for Anti-Smoking Treatment (originally issued in March 2006 by the Japanese Circulation Society, Japan Lung Cancer Society, and Japanese Cancer Association). The patients were treated with transdermal nicotine patches or the oral administration of varenicline. Among patients who attended our smoking cessation clinic, 56 (37 males and 19 females) successfully quit smoking. We measured their serum leptin and adiponectin levels at baseline, 3 months, and 1 year after beginning smoking cessation. Moreover, the changes in data from before to 3 months and 1 year after smoking cessation were compared by unpaired t-test between patients with a WC increase smaller than the median and those with a WC increase greater than the median. Results: Body mass index and WC significantly increased from baseline to 3 months to 1 year after beginning smoking cessation. The leptin level significantly increased (5.0 ng/ml → 6.2 ng/ml (p < 0.05) → 7.1 ng/ml (p < 0.001)) in proportion to the weight gain. Adiponectin levels, however, did not change after smoking cessation. Using the median ΔWC (+1.8 %) as the cutoff point, patients were divided into two groups. The percent change in adiponectin level from baseline to 1 year was significantly greater in the ΔWC < median group (+13.4 %) than in the ΔWC ≧ median group (-0.6 %) (p = 0.028). Conclusion: Despite weight gain and increased abdominal obesity, serum adiponectin levels did not decrease after smoking cessation. Rather, they increased at 1 year after smoking cessation in patients with less abdominal obesity. Thus, the beneficial effect of smoking cessation may outweigh the adverse effect of weight gain after smoking cessation.

Creatinine clearance (CrCl) has been widely used to adjust the dosage of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation (AF) and exclude contraindicated patients. However, there are few available real-world data on the relation between CrCl and adverse clinical outcomes in patients with AF. Therefore, we evaluated the clinical characteristics and adverse events in Japanese patients with AF stratified by CrCl. We categorized patients in the Fushimi AF Registry, a large prospective community-based Japanese cohort of patients with AF, into 3 groups as follows: (1) CrCl

Although cardiovascular risks decrease after quitting smoking, body weight often increases in the early period after smoking cessation. We have previously reported that the serum level of the α1-antitrypsin–low-density lipoprotein complex (AT–LDL)—an oxidatively modified low-density lipoprotein that accelerates atherosclerosis—is high in current smokers, and that the level rapidly decreases after smoking cessation. However, the effects of weight gain after smoking cessation on this cardiovascular marker are unknown. In 183 outpatients (134 males, 49 females) who had successfully quit smoking, serum AT–LDL levels were measured using an enzyme-linked immunosorbent assay. For all persons who had successfully quit smoking, body mass index (BMI) significantly increased 12 weeks after the first examination (p

A natural p300-specific histone acetyltransferase inhibitor, curcumin, may have a therapeutic potential for heart failure. However, a study of curcumin to identify an appropriate dose for heart failure has yet to be performed. Rats were subjected to a left coronary artery ligation. One week later, rats with a moderate severity of myocardial infarction (MI) were randomly assigned to 4 groups receiving the following: a solvent as a control, a low dose of curcumin (0.5 mg∙kg−1∙day−1), a medium dose of curcumin (5 mg∙kg−1∙day−1), or a high dose of curcumin (50 mg∙kg−1∙day−1). Daily oral treatment was continued for 6 weeks. After treatment, left ventricular (LV) fractional shortening was dose-dependently improved in the high-dose (25.2% ± 1.6%, P < 0.001 vs. vehicle) and medium-dose (19.6% ± 2.4%) groups, but not in the low-dose group (15.5% ± 1.4%) compared with the vehicle group (15.1% ± 0.8%). The histological cardiomyocyte diameter and perivascular fibrosis as well as echocardiographic LV posterior wall thickness dose-dependently decreased in the groups receiving high and medium doses. The beneficial effects of oral curcumin on the post-MI LV systolic function are lower at 5 compared to 50 mg∙kg−1∙day−1 and disappear at 0.5 mg∙kg−1∙day−1. To clinically apply curcumin therapy for heart failure patients, a precise, optimal dose-setting study is required. Keywords:: curcumin, heart failure, hypertrophy, dose-dependency, p300

Aim Previous epidemiological studies demonstrated that the ratio of n-6 to n-3 polyunsaturated fatty acids is associated with cardiovascular diseases. We herein investigated whether the beneficial effect of highly purified eicosapentaenoic acid(EPA) on arterial stiffness is associated with changes in the ratio of polyunsaturated fatty acids, such as EPA, docosahexaenoic acid(DHA) and dihomo-γ-linolenic acid(DGLA), relative to arachidonic acid(AA), in obese Japanese patients with dyslipidemia. Methods The EPA/AA, DHA/AA and DGLA/AA ratios were compared between obese patients with(n=94) and without (n=31) dyslipidemia. Among the former group, 88 patients received either highly purified EPA treatment(1.8g daily, n=45) or treatment without EPA(control, n=43). Results At baseline, the ratios of DHA/AA and DGLA/AA were significantly(P＜0.05) higher in obese patients with dyslipidemia than in those without, while the EPA/AA ratio was similar between patients with and without dyslipidemia. EPA significantly reduced the hemoglobin A1c, total cholesterol, triglycerides, CRP, cardio-ankle vascular index(CAVI)(an index of arterial stiffness) and the DGLA/AA ratio relative to the control at three months after the treatment. On the other hand, EPA significantly increased the adiponectin level and EPA/AA ratio(P＜0.05). A multivariate regression analysis revealed that only age, an increase in the EPA/AA ratio and a decrease in the CRP level were significant determinants of a reduction of the CAVI by EPA. Conclusion These findings suggest that EPA improves the arterial stiffness in association with an increase in the EPA/AA ratio and a decrease in inflammation in obese patients with dyslipidemia.

Management of atrial fibrillation (AF) with current rhythm-control therapy has an uncertain impact on outcomes. Among 3731 patients in the Fushimi AF Registry, a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, we investigated the characteristics and outcomes in 478 patients receiving rhythm-control therapy (anti-arrhythmic drug and/or catheter ablation) alone, with 1279 patients receiving rate-control therapy (beta-blockers, calcium channel blockers, and digoxin) alone serving as a reference. The Rhythm-control group, 26% of which had prior catheter ablation, was younger (70.5 ± 10.8 vs. 74.3 ± 10.4 years, P < 0.001) with lower CHA 2DS 2-VASc score (2.71 ± 1.63 vs. 3.64 ± 1.62, P < 0.001) and received oral anticoagulants less frequently than the Rate-control group. During the median follow-up of 1107 days, the incidence of the composite of cardiac death and heart failure (HF) hospitalization was lower with rhythm control (hazard ratio (HR) 0.24, 95% confidence interval (CI) 0.14–0.36; P < 0.001), whereas that of ischemic stroke/systemic embolism was not significantly different (HR 0.64, 95% CI 0.35–1.10; P = 0.12), when compared to rate control. Propensity score-matching analysis as well as multivariate analysis further supported the relation of Rhythm-control group to the lower incidence of the composite of cardiac death and HF hospitalization. Rhythm-control therapy by anti-arrhythmic drug and/or catheter ablation in the contemporary clinical practice was associated with the lower incidence of the composite of cardiac death and HF hospitalization, as compared with rate-control therapy in a Japanese AF cohort. However, given the fundamental differences in baseline clinical characteristics between the rhythm- and Rate-control groups, the results cannot be generalizable.

Glucagon-like peptide-1 (GLP-1) exerts beneficial effects on the cardiovascular system. Here, we examined the effect of sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, on systemic inflammation and pro-inflammatory (M1)/anti-inflammatory (M2)-like phenotypes of peripheral blood monocytes in diabetic patients.Forty-eight type 2 diabetic patients were divided into the following two groups: sitagliptin-treatment (50mg daily for 3months) (n=24) and untreated control (n=24) groups. Measurements were undertaken to assess changes in glucose-lipid metabolism, serum levels of inflammatory cytokines such as serum amyloid A-LDL (SAA-LDL), C-reactive protein (CRP), interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α). Furthermore, the effects of sitagliptin treatment on M1/M2-like phenotypes in peripheral blood monocytes were examined.Treatment with sitagliptin significantly decreased fasting plasma glucose, hemoglobin A1c (HbA1c), serum levels of inflammatory markers, such as SAA-LDL, CRP, and TNF-α. In contrast, sitagliptin increased serum IL-10, an anti-inflammatory cytokine, as well as plasma GLP-1. In addition, sitagliptin increased monocyte IL-10 expression and decreased monocyte TNF-α expression. Multivariate regression analysis revealed that the sitagliptin treatment was the only factor independently associated with an increase in monocyte IL-10 (β=0.499; R(2)=0.293, P0.05). However, other factors including the improvement of glucose metabolism were not associated with the increase.This study is the first to show that a DPP-4 inhibitor, sitagliptin, reduces inflammatory cytokines and improves the unfavorable M1/M2-like phenotypes of peripheral blood monocytes in Japanese type 2 diabetic patients.

AIM: Smoking induces vascular inflammation and increases the risk of cardiovascular events. Lectinlike oxidized low-density lipoprotein receptor-1 (LOX-1) is a scavenger receptor that is induced by oxidative stress and is associated with atherosclerotic plaque formation and destabilization. LOX-1 interacts with C-reactive protein (CRP) and plays an important role in inflammatory diseases. We therefore hypothesized that LOX-1 may be involved in the onset of smoking-induced vascular inflammation. METHODS: We measured the soluble LOX-1 (sLOX-1) levels in sera obtained from 207 current smokers. RESULTS: The serum sLOX-1 levels positively correlated with various smoking variables, such as the number of cigarettes smoked per day (r= 0.150, p