Elevated RANTES level is associated with metabolic syndrome and correlated with activated platelets associated markers in healthy younger men.

The objective of this study was to clarify the relationship of regulated on activation normal T cell expressed and secreted (RANTES) levels with metabolic syndrome (MS) and activated platelets-associated markers. We conducted a cross-sectional study of 210 healthy Japanese male volunteers (mean age 41 years old) who did not take any medications and were free of cardiovascular or cerebrovascular disease. The RANTES is correlated with age, diastolic blood pressure, and fast glucose by multivariate analysis using the cardiovascular risk factors (R (2) = .396, P < .001). The plasma RANTES level is significantly associated with MS after adjusting for age (P = .040). Once plasma interleukin 6, an activator of platelets, and plasma platelet-derived microparticles, a marker for activated platelets, are put into the equation, plasma RANTES level is significantly correlated with the activated platelet-associated markers (R (2) = .396, P < .001). These suggest the possible role of elevated RANTES in the forerunner of atherosclerosis in healthy younger men.

Effects of pitavastatin on plasminogen activator inhibitor-1 in hyperlipidemic patients.

The effects of statins on two platelet activation markers, plasiminogen activator inhibitor (PAI)-1 and adiponectin, were investigated in 68 patients with hyperlipidemia. The patients were treated with pitavastatin with a dosage of 2 mg daily. The plasma levels of platelet-derived microparticles (PDMP), soluble CD40 ligand (sCD40L), sP-selectin, PAI-1, and adiponectin were measured at baseline and after 6 months of treatment in both groups. In hyperlipidemic patients, the plasma levels were higher in PDMP, sCD40L, sP-selectin, and PAI-1, and lower in adiponectin, compared to the normolipidemic controls. Plasma PDMP and sCD40L were positively correlated, while plasma adiponectin was negatively correlated with the plasma levels of PAI-1. No significant differences were observed in the plasma levels of PDMP, sCD40L, sP-selectin, and PAI-1 before and after treatment. A significant increase in plasma adiponectin levels was observed after 6 months of treatment with pitavastatin. When the patients treated with pitavastatin were divided into two groups according to the adiponectin response to pitavastatin treatment, significant decreases in plasma PAI-1, PDMP, and sCD40L levels were observed after pitavastatin treatment in the responder group. These findings suggest that PDMP, sCD40L, and PAI-1 may participate in the development of atherothrombosis in patients with hyperlipidemia, and that pitavastatin may exert an adiponectin-dependent anti-atherothrombotic effect in hyperlipidemic patients.

Plasma level of platelet-derived microparticles is associated with coronary heart disease risk score in healthy men.

AIM: The aim of this study was to clarify the relationship between platelet-derived microparticles (PDMPs) and the Framingham 10-yr coronary heart disease (CHD) risk score. METHODS: A cross-sectional study of healthy volunteers free of medication, and cardiovascular or cerebrovascular disease was conducted. The subjects were 190 Japanese men (median age 41). An ELISA kit and monoclonal antibodies against CD42b and CD42a (glycoprotein Ib and IX) were used. RESULTS: PDMPs are correlated with platelet count, high sensitivity C-reactive protein (hsCRP), and diastolic blood pressure by multivariate analysis (R(2)=0.316, p <0.001). Quartile range of PDMPs is significantly associated with the 10-yr CHD risk score after adjusting for age, platelet count, hsCRP, and hypertension (p=0.033) and for age, platelet count, hsCRP, and presence of metabolic syndrome (MS) (p=0.020). In individuals with a predicted 10-yr risk for CHD >or=8% (corresponding with the highest quartile), compared to those with a predicted 10-yr risk <8%, the odds ratio (OR), adjusted for age, platelet count, hsCRP, and hypertension, was 3.3 (1.2-8.9) and adjusted for age, platelet count, hsCRP, and MS, was 4.5 (1.6-11.8). The age-, platelet count-, hsCRP- and hypertension-adjusted OR for a 10-yr CHD risk score >or=8% was 0.8 (0.5-1.3) for hsCRP and 3.9 (1.6-9.4) for hypertension. The age-, platelet count-, hsCRP- and MS -adjusted OR for a 10-yr CHD risk score >or=8% was 0.7 (0.4-1.2) for hsCRP and 7.9 (2.6-24.5) for MS. CONCLUSION: Elevated PDMPs are associated with the 10-yr CHD risk score in healthy men.

Correlation and association of plasma interleukin-6 and plasma platelet-derived microparticles, markers of activated platelets, in healthy individuals.

INTRODUCTION: The aim of this study was to clarify the correlation and association of plasma IL-6 and PDMPs, both of which are associated with metabolic syndrome, in healthy individuals. MATERIALS AND METHODS: We conducted a cross-sectional study of 464 healthy Japanese volunteers (210 men and 254 women, median age 39 and 35years, respectively) who had no signs, symptoms or history of cardiovascular- or cerebrovascular disease and took no medications. We assayed their IL-6 levels with a conventional ELISA kit and their PDMP levels by ELISA and monoclonal antibodies against CD42b and CD42a (glycoprotein Ib and IX). RESULTS: By multivariate analysis, the plasma level of PDMP was correlated with diastolic blood pressure (p=0.015), platelet count (p<0.001), high sensitivity C-reactive protein, and the plasma level of IL-6 (p<0.001) in men (R(2)=0.454, p<0.001) and was correlated with platelet count (p<0.001) and the plasma level of IL-6 (p<0.001) in women (R(2)=0.159, p<0.001). Quartile range of plasma level of IL-6 was associated with plasma level of PDMP after adjustment for diastolic blood pressure, platelet count, and high sensitivity C-reactive protein in men (p<0.001) and associated with plasma level of PDMP after adjustment for platelet count in women (p<0.001). CONCLUSIONS: These results suggest the plasma IL-6 is correlated and associated with the plasma PDMPs, markers of activated platelets in healthy individuals.

Soluble TRAIL prevents RANTES-dependent restenosis after percutaneous coronary intervention in patients with coronary artery disease.

Some factors play pathogenic roles in the development of restenosis after percutaneous coronary intervention (PCI). We measured and compared the ratio of elevated levels of regulated on activation normally T-cell expressed and secreted (RANTES), soluble (s) P-selectin, sE-selectin, s vascular cell adhesion molecule (VCAM)-1, s interleukin-2 receptor (IL-2R) and s tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) after PCI. Plasma levels of chemokines and soluble markers were measured before and 30 days after PCI in 85 patients (61 males and 24 females, aged 61 +/- 7 years) who underwent PCI and who had repeated angiograms at a 6-month follow-up. Restenosis occurred in 29 (34.1%) patients. The significant and time-dependent increases in RANTES, sIL-2R and sVCAM-1 were observed in the restenosis group. However, there were no significant differences in sP-selectin and sE-selectin levels with or without restenosis. sTRAIL levels in patients with coronary artery disease were significantly higher than levels in normal controls. Furthermore, unlike the restenosis group, sTRAIL levels after PCI were significantly increased in the non-restenosis group, and sTRAIL levels correlated significantly with sVCAM-1 and sE-selectin. These findings suggest that restenosis development after PCI in patients with coronary artery disease involve the participation of RANTES and activated T-lymphocyte expressing CD25 after PCI, and sTRAIL may prevent this RANTES-dependent restenosis.

Correlation and association between plasma platelet-, monocyte- and endothelial cell-derived microparticles in hypertensive patients with type 2 diabetes mellitus.

Elevated platelet-derived mircoparticles (MP) (PDMP), endothelial cell-derived MP (EDMP), and monocyte-derived MP (MDMP) concentrations are documented in almost all thrombotic diseases. However, the intricate interactions between PDMP, MDMP and EDMP in hypertensive patients with or without type 2 diabetes remains poorly understood. Therefore, to clarify the correlation and association of MPs, we measured and analysed the levels of MPs in 359 hypertensive patients. We compared the results of chemokines, cell adhesion molecules, platelet activation markers and microparticles in hypertensive patients with and without type 2 diabetes mellitus. The levels of all markers were significantly higher in the hypertensive patients with diabetes than in the non-diabetic patients. For hypertensive patients with diabetes, univariate analysis showed that age, body mass index, systolic blood pressure, high density lipoprotein cholesterol (HDL-CHO), creatinine (CRTN), soluble P-selectin (sP-selectin), soluble E-selectin (sE-selectin), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble CD40 ligand (sCD40L), regulated on activation normally T-cell expressed and secreted (RANTES), monocyte chemotactic peptide-1 (MCP-1), MDMP and EDMP were significantly associated with PDMP. In addition, systolic blood pressure, HDL cholesterol, sP-selectin, sE-selectin, sVCAM-1, sCD40L, RANTES, MDMP and EDMP were significant factors in the multivariate model with PDMP. Furthermore, a correlation between plasma PDMP and MDMP or EDMP in hypertensive patients were observed both with and without diabetes. These results suggest that the existence of diabetes mellitus affects PDMP generation in hypertensive patients and that enhanced plasma levels of PDMP and an association between the plasma levels of PDMP, MDMP and EDMP may result in the development of atherothrombotic complications in hypertensive patients.

The significance of EMAP-II after allogeneic stem cell transplantation.

Endothelial monocyte-activating polypeptide-II (EMAP-II) appears to play an important role in neovascularization and endothelial abnormalities. However, the role of EMAP-II in development of graft-versus-host disease (GVHD) after allogeneic SCT is poorly understood. We measured and compared the levels of EMAP-II, cytokines, and soluble factors in patients undergoing allogeneic SCT. The subjects were 23 patients who underwent allogeneic SCT. Most of the cytokines/soluble factors exhibited a significant elevation after allogeneic SCT, although Angiopoietin-1 did not change. On the other hand, the levels of these factors did not change significantly in the recipients of autologous SCT. When the relationship between EMAP-II and cytokines/soluble factors was analyzed, EMAP-II levels correlated positively with sIL-2R, sVCAM-1, sE-selectin, sFasL and EDMP. However, IL-6, Angiopoietin-1, Angiopoietin-2 and VEGF were not correlated with EMAP-II. Our results suggest that EMAP-II plays an important role in endothelial cell dysfunction related to GVHD after allogeneic SCT.

Effects of pitavastatin on monocyte chemoattractant protein-1 in hyperlipidemic patients.

The effects of statins on platelet activation markers, chemokines and adiponectin, were investigated in 135 patients with hyperlipidemia. Of the 135 hyperlipidemic patients, 63 were allocated to the simvastatin group, treated with simvastatin at the dose of 10 mg daily, and the remaining 72 were allocated to the pitavastatin group, treated with pitavastatin at the dose of 2 mg daily. Plasma levels of platelet-derived microparticles (PDMP), cell adhesion molecules (sCD40L and sP-selectin), chemokines [monocyte chemoattractant protein-1 (MCP-1) and regulated on activation normally T-cell expressed and secreted] and adiponectin were measured at the baseline and after 6 months of treatment in both the groups. In addition, we carried out a basic study to investigate the MCP-1-dependent induction of tissue factor expression on a histiocytic cell line (U937 cells). The plasma levels of PDMP, sCD40L, sP-selectin, regulated on activation normally T-cell expressed and secreted and MCP-1 were higher, whereas those of adiponectin were lower, in the hyperlipidemic patients than in the normolipidemic controls. Plasma PDMP and sCD40L were positively correlated, whereas plasma adiponectin was negatively correlated, with the plasma levels of MCP-1. No significant differences in the plasma levels of PDMP, sCD40L, sP-selectin, regulated on activation normally T-cell expressed and secreted and MCP-1 measured before and after treatment were observed in either the simvastatin or pitavastatin group. A significant increase of the plasma adiponectin levels was observed after 6 months of treatment with pitavastatin but not after an equal duration of treatment with simvastatin. When pitavastatin-treated patients were divided into two groups according to the adiponectin response to pitavastatin treatment, significant decreases of the plasma MCP-1, PDMP and sCD40L levels were observed after pitavastatin treatment in the responder group. In the aforementioned basic study, MCP-1 by itself did not induce the expression of tissue factor on the U937 cells. However, the recombinant sCD40L-induced expression of tissue factor on U937 was enhanced by the addition of MCP-1. These findings suggest that PDMP, sCD40L and MCP-1 may participate in the development of atherothrombosis in patients with hyperlipidemia and that pitavastatin may exert an adiponectin-dependent antiatherothrombotic effect in hyperlipidemic patients.

Effects of eicosapentaenoic acid on endothelial cell-derived microparticles, angiopoietins and adiponectin in patients with type 2 diabetes.

AIM: The aim of this study was to evaluate the significance of endothelial cell-derived microparticles (EDMP), angiopoietin-2 (Ang-2) and adiponectin in hyperlipidemic patients with and without type 2 diabetes mellitus, and to compare the two for the effects of eicosapentaenoic acid (EPA) on these markers. METHODS: One hundred and twenty-six hyperlipidemic patients with and without type 2 diabetes mellitus received EPA 1,800 mg daily, and 50 of the patients were non-diabetic. RESULTS: EDMP and Ang-2 levels prior to treatment were higher in diabetic patients than in non-diabetic patients, whereas adiponectin levels were lower in diabetics. When diabetic patients were classified into two groups on the basis of Ang-2 levels, the levels of all markers remained unchanged in those without a high Ang-2 level after EPA treatment. In contrast, all markers except for adiponectin were decreased significantly in diabetic patients with high Ang-2 levels after 6 months of EPA treatment. These diabetic patients with high Ang-2 levels displayed a more significant increase in adiponectin levels after EPA treatment than those who did not. CONCLUSION: These results suggest that EPA possesses an adiponectin-dependent anti-atherosclerotic effect and may be beneficial for the prevention of vascular complications in diabetic patients with high Ang-2 levels.

Effect of acarbose on platelet-derived microparticles, soluble selectins, and adiponectin in diabetic patients.

Platelet-derived microparticles (PDMP), selectins, and adiponectin play an important role in the development of atherosclerosis in diabetes. Acarbose has been shown to have a beneficial effect on postprandial hyperglycemia in diabetic patients. However, its influence on PDMP, selectins, and adiponectin in these patients is poorly understood. We investigated the effect of acarbose on circulating levels of PDMP, selectins, and adiponectin in patients with type 2 diabetes. Acarbose (300 mg/day) was administered for 3 months. Levels of PDMP, sP-selectin, sL-selectin, and adiponectin were measured by ELISA at baseline and after 1 and 3 months of treatment. The levels of PDMP, sP-selectin, and sL-selectin were higher in diabetic patients than in hypertensive patients (PDMP; 35.1 +/- 34.2 vs. 53.3 +/- 56.7 U/ml, P < 0.05: sP-selectin; 134 +/- 52 vs. 235 +/- 70 ng/dl, P < 0.01: sL-selectin; 569 +/- 183 vs. 805 +/- 146 ng/ml, P < 0.05), while there were no significant differences between hypertensive and hyperlipidemic patients. Before acarbose treatment, the adiponectin level of diabetic patients was lower than that of hypertensive patients. Acarbose therapy significantly decreased the plasma PDMP level relative to baseline. Acarbose also caused a significant decrease of sP-selectin and sL-selectin. On the other hand, acarbose therapy led to a significant increase of adiponectin after 3 months of administration compared with baseline (adiponectin: diabetes versus hypertension, 3.61 +/- 1.23 vs. 5.87 +/- 1.92 microg/ml, P < 0.05; diabetes versus controls, 2.81 +/- 0.95 vs. 6.13 +/- 1.24 microg/ml, P < 0.01). Twelve of the 30 diabetic patients had a history of thrombotic complications. Furthermore, the reduction of PDMP and selectins during acarbose therapy was significantly greater in the thrombotic group (12 of 30) than in the nonthrombotic group (18 of 30) of diabetic patients. Acarbose may be beneficial for primary prevention of atherothrombosis in patients with type 2 diabetes. However, it requires a large clinical trial to test this hypothesis.

The effects of pitavastatin, eicosapentaenoic acid and combined therapy on platelet-derived microparticles and adiponectin in hyperlipidemic, diabetic patients.

Platelet-derived microparticles (PDMP) play an important role in the pathogenesis of diabetic vasculopathy, and statins or eicosapentaenoic acid (EPA) have been shown to have a beneficial effect on atherosclerosis in hyperlipidemic patients. However, the influence of EPA and statins on PDMP and adiponectin in atherosclerosis is poorly understood. We investigated the effect of pitavastatin and EPA on circulating levels of PDMP and adiponectin in hyperlipidemic patients with type II diabetes. A total of 191 hyperlipidemic patients with type II diabetes were divided into three groups: group A received pitavastatin 2 mg once daily (n = 64), group B received EPA 1800 mg daily (n = 55) and group C received both drugs (n = 72). PDMP and adiponectin were measured by ELISA at baseline and after 3 and 6 months of drug treatment. Thirty normolipidemic patients were recruited as healthy controls. PDMP levels prior to treatment in hyperlipidemic patients with diabetes were higher than levels in healthy controls (10.4 +/- 1.9 vs. 3.1 +/- 0.4 U/ml, p < 0.0001), and adiponectin levels were lower than controls (3.20 +/- 0.49 vs. 5.98 +/- 0.42 microg/ml, p < 0.0001). PDMP decreased significantly in group B (before vs. 6M, 10.6 +/- 2.0 vs. 8.0 +/- 1.7 U/ml, p < 0.01), but not in group A (before vs. 6M, 9.4 +/- 1.9 vs. 9.6 +/- 1.7 U/ml, not significant). In contrast, group A exhibited a significant increase in adiponectin levels after treatment (before vs. 6M, 3.29 +/- 0.51 vs. 4.16 +/- 0.60 microg/ml, p < 0.001). Furthermore, group C exhibited significant improvement in both PDMP and adiponectin levels after treatment (PDMP, before vs. 6M, 11.2 +/- 2.0 vs. 4.5 +/- 2.7 U/ml, p < 0.001; adiponectin, before vs. 6M, 3.24 +/- 0.41 vs. 4.02 +/- 0.70 microg/ml, p < 0.001). Reductions of PDMP in combined therapy were significantly greater than those observed with EPA alone (p < 0.05 by ANOVA). In addition, soluble CD40 ligand exhibited almost the same change as PDMP in all therapy groups. These results suggest that pitavastatin possesses an adiponectin-dependent antiatherosclerotic effect, and this drug is able to enhance the anti-platelet effect of EPA. The combination therapy of pitavastatin and EPA may be beneficial for the prevention of vascular complication in hyperlipidemic patients with type II diabetes.

Significance of soluble CD40 ligand, adiponectin and reactive oxygen metabolites in aging.

We analyzed the association between platelet activation, adiponectin, insulin resistance and oxidative stress in aging. In addition, we included American football (AB) players to investigate whether this association is modulated by exercise. Eighty-six old age patients (> or = 65 years old) hospitalized at the nursing institution and 62 AB players were recruited as study subjects. Reactive oxygen metabolites (ROM), soluble CD40 ligand (sCD40L) and adiponectin were estimated with these patients. In comparison to old age, plasma adiponectin levels in AB players were significantly low. In addition, the adiponectin values of elder group (> 80 years) in old age were significantly increased higher than those for younger group (< or = 80 years). There were no differences of sCD40L in two groups. Levels of ROM in AB players were also significantly lower than that in old age. However, the ROM values of younger group in old age were significantly increased higher than those for elder group. The sCD40L also exhibited the same results. There were no significant differences in ROM and adiponectin levels between the high homeostasis model assessment-insulin resistance (HOMA-IR) (> 2.0) and the low HOMA-IR (< or = 2.0). In contrast, in the old age, the sCD40L and ROM levels in the high HOMA-IR group were significantly higher than those in the low HOMA-IR group. In addition, the adiponectin level in the high HOMA-IR group was significantly lower than that in the low HOMA-IR group. Our results suggest that platelet activation, adiponectin and oxidative stress are the very important factors for aging, and the maintenance of exercise could prevent the occurrence of metabolic syndrome or insulin resistance.

Evaluation of angiopoietins and cell-derived microparticles after stem cell transplantation.

Although stem cell transplantation (SCT) is being used for hematopoietic reconstitution following high-dose chemotherapy for malignancy, it involves certain serious transplant-related complications such as graft-versus-host disease (GVHD). Angiopoietins play important roles in angiogenesis. However, the role of angiopoietins after SCT is poorly understood. In this study, 52 patients underwent SCT; 26 patients received allogeneic SCT, while the remaining 26 received autologous SCT. In 48 of 52 patients, levels of angiopoietins, cytokines, and soluble factors were measured by enzyme-linked immunosorbent assay. Soluble Fas ligand (sFasL) and endothelial cell-derived microparticle (EDMP) exhibited significant elevation in the early phase (2-3 weeks) after SCT. In addition, the elevation of interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and sIL-2 receptor (sIL-2R), which are GVHD markers after allogeneic SCT was observed. The level of angiopoietin (Ang)-2 in allogeneic SCT continued to increase for up to 4 weeks, although the level of Ang-1 did not show significant changes. The patients with high Ang-2 exhibited significant increase of sFasL and EDMP compared with those with low Ang-2. In addition, the patients with high-grade GVHD exhibited a significant increase in Ang-2 compared to patients with low-grade GVHD. In the in vitro experiment using endothelial cells, the suppressive effect of Ang-1 on EDMP generation by TNF-alpha was partially inhibited by the addition of Ang-2. Furthermore, multivariate regression analysis showed that EDMP and sFasL were significant factors in Ang-2 elevation. Our results suggest that Ang-2 generation after allogeneic SCT relates to GVHD.

Significance of microparticles in progressive systemic sclerosis with interstitial pneumonia.

We measured and compared the levels of microparticles, chemokines, cell adhesion molecules and platelet activation markers with a view to developing a better understanding of their potential contributions to the pathophysiology of progressive systemic sclerosis (PSS, scleroderma). The concentrations of all the factors in PSS patients were significantly higher than those in normal subjects. PSS patients were divided to two groups by whether they have interstitial pneumonia (IP) or not. There were no differences in the levels of soluble(s) VCAM-1, sICAM-1, sE-selectin and IL-8 between the two groups. However, there were significant between-group differences in the levels of sP-selectin, sCD40L, ENA-78, RANTES (regulated on activation normally T-cell expressed and secreted), platelet-derived microparticles (PDMPs), monocyte-derived microparticle (MDMPs) and KL-6. The level of tissue factor expression on monocytes by A23187 stimulation in PSS patients was found to be similar to that in healthy controls. Although PDMP did not induce the expression of tissue factor on monocytic cell line (THP-1) directly, the recombinant sCD40 ligand-induced expression of tissue factor on THP-1 and generation of MDMP from this cell line were enhanced by the addition of PDMPs. Our findings suggested that elevated levels of PDMPs and MDMPs may be interpreted as a sign of vascular complications in PSS patients, particularly those complicated with IP, offering a new treatment strategy in these patients.

Correlation between adiponectin and reduction of cell adhesion molecules after pitavastatin treatment in hyperlipidemic patients with type 2 diabetes mellitus.

The aim of this study was to determine whether pitavastatin may prevent the progression of atherosclerotic changes in hyperlipidemic patients. Seventy-five hyperlipidemic patients with and without type 2 diabetes were enrolled to receive pitavastatin 2 mg daily. Cell adhesion molecules (sCD40L, sP-selectin, sE-selectin, and sL-selectin), chemokines (MCP-1 and RANTES) and adiponectin were measured at baseline and after 3 and 6 months of pitavastatin treatment. Adiponectin levels prior to pitavastatin treatment in hyperlipidemic patients with and without diabetes were lower than levels in normolipidemic controls. Both total cholesterol and the LDL-cholesterol (LDL-C) decreased significantly after pitavastatin administration. Additionally, hyperlipidemic patients with type 2 diabetes exhibited a significant increase in adiponectin levels after pitavastatin treatment (before vs. 3 months, 6 months, 2.81+/-0.95 vs. 3.84+/-0.84 microg/ml (p<0.01), 4.61+/-1.15 mug/ml (p<0.001)). Furthermore, hyperlipidemic diabetics exhibited significant decreases in sE-selectin and sL-selectin levels after 6 months of pitavastatin treatment (sE-selectin, before vs. 6 months, 74+/-21 vs. 51+/-10 ng/ml, p<0.05; sL-selectin, before vs. 6 months, 896+/-141 vs. 814+/-129 ng/ml, p<0.05). In addition, adiponectin showed significant correlation with sE-selectin and sL-selectin in diabetic hyperlipidemia. However, MCP-1, RANTES and sCD40L did not exhibit any differences before or after pitavastatin administration. These results suggest that pitavastatin possesses an adiponectin-dependent anti-atherosclerotic effect in hyperlipidemic patients with type 2 diabetes in addition to its lowering effects on total cholesterol and LDL-C.

Role of soluble tumor necrosis factor-related apoptosis-inducing ligand concentrations after stem cell transplantation.

Although stem cell transplantation (SCT) is being used for hematopoietic reconstitution following high-dose chemotherapy for malignancy, it involves certain serious transplant-related complications such as graft-versus-host disease (GVHD). Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) plays important roles in regulating cell death, immune response, and inflammation. However, the role of soluble TRAIL (sTRAIL) after SCT is poorly understood. In this study, 42 patients underwent SCT; 22 patients received allogeneic SCT, while the remaining 20 received autologous SCT. In these patients, levels of sTRAIL, cytokines, and soluble factors were measured by enzyme-linked immunosorbent assay (ELISA). In addition, a basic study of the generation of endothelial cell-derived microparticle (EDMP) by TNF-alpha and soluble Fas ligand (sFasL) was conducted. sFasL and EDMP exhibited significant elevation in the early phase (2-3 weeks) after SCT. In addition, the elevation of IL-6, TNF-alpha, and sIL-2R after allogeneic SCT was observed. EDMP also exhibited changes similar to sFasL. The patients with high sTRAIL exhibited significant decrease of sFasL and EDMP as compared with those without high sTRAIL. TNF-alpha and sFasL induced an increase in procoagulant and apoptotic markers in endothelial cells, and EDMP shedding was observed. Furthermore, sTRAIL inhibited the EDMP elevation caused by TNF-alpha and sFasL. The apoptotic markers such as sFasL and sTRAIL exhibited particular changes after SCT. Our results suggest that sTRAIL generation after allogeneic SCT relates to the prevention of GVHD.

Evaluation of platelet and leukocyte functions in effort angina patients using high shear conditions in small-sized collagen bead columns.

This study used a small-sized collagen bead column system to investigate platelet functions under high shear stress in 28 patients with effort angina and 15 healthy controls. Soluble P-selectin and soluble L-selectin were also evaluated. Patients underwent stent insertion, followed by treatment with aspirin (100 mg/day) and ticlopidine (200 mg/day). High-shear-dependent platelet function was measured using small-sized collagen beads. The retention rate of platelets from patients with angina was higher than that in healthy controls (10.9% +/- 3.9% versus 5.6% +/- 1.7%, P < .01). Soluble P-selectin and soluble L-selectin levels of patients with angina significantly increased after passage through the columns. Levels of soluble P-selectin and L-selectin in healthy controls did not exhibit significant changes with passage through the columns. These results suggested that high shear stress caused abnormal activation of leukocytes or adhesive proteins in patients with effort angina, and ticlopidine failed to suppress hyperaggregability of platelets in these patients.