Transthyretin (

The granulocyte colony-stimulating factor (G-CSF) promotes angiogenesis. However, the exact mechanism is not known. We demonstrate that vascular endothelial growth factor (VEGF) was released by Gr-1+CD11b- neutrophils but not Gr-1-CD11b+ monocytes prestimulated with G-CSF in vitro and in vivo. Similarly, in vivo, concomitant with an increase in neutrophil numbers in circulation, G-CSF augmented plasma VEGF level in vivo. Local G-CSF administration into ischemic tissue increased capillary density and provided a functional vasculature and contributed to neovascularization of ischemic tissue. Blockade of the VEGF pathway abrogated G-CSF-induced angiogenesis. On the other hand, as we had shown previously, VEGF can induce endothelial progenitor cell (EPC) mobilization. Here, we show that G-CSF also augmented the number of circulating VEGF receptor-2 (VEGFR2) EPCs as compared with untreated controls. Blocking the VEGF/VEGFR1, but to a much lesser extent, the VEGF/VEGFR2 pathway in G-CSF-treated animals delayed tissue revascularization in a hindlimb model. These data clearly show that G-CSF modulates angiogenesis by increasing myelomonocytic cells (VEGFR1+ neutrophils) and their release of VEGF. Our results indicated that administration of G-CSF into ischemic tissue provides a novel and safe therapeutic strategy to improve neovascularization.

Objective: To investigate whether concentrations of plasma adiponectin constitute a significant coronary risk factor, with particular focus on the relation between plasma concentrations of adiponectin and the development of acute coronary syndrome (ACS). Subjects and methods: Plasma concentrations of adiponectin were measured in 123 patients with coronary artery disease (CAD) and in 17 control participants. Patients were divided into three groups according to condition type: acute myocardial infarction (AMI) group (n = 59), unstable angina pectoris (UAP) group (n = 28), and stable angina pectoris (SAP) group (n = 36). Results: Plasma concentrations of adiponectin correlated negatively with body mass index (r = 20.18, p , 0.05), serum triglyceride (r = 20.25, p , 0.01), and fasting glucose concentrations (r = 20.21, p , 0.05), but correlated positively with age (r = 0.26, p , 0.01), high density lipoprotein cholesterol concentrations (r = 0.35, p , 0.01), and low density lipoprotein particle size (r = 0.37, p , 0.01). Plasma concentrations of adiponectin in patients with ACS, in both the AMI and UAP groups, were significantly lower than those in patients with SAP and in the control group (ACS, 6.5 (3.0) mg/ml; SAP, 11.3 (5.9) mg/ml; control 12.8 (4.3) mg/ml; p , 0.01). Additionally, plasma concentrations of adiponectin in patients with CAD (7.9 (4.6) mg/ml, p , 0.01) were significantly lower than in the control group. There were, however, no significant differences between patients with SAP and the control group (p = 0.36). Multiple logistic regression analysis showed that smoking, fasting glucose concentration, and low log adiponectin concentration correlated independently with the development of an ACS. Conclusions: The findings suggest that measurement of plasma concentrations of adiponectin may be of use for assessing the risk of CAD and may be related to the development of ACS.

Among Japanese men with BMI of 23-25 kg/m, muscle insulin resistance was present in those with even one CMRF. In this population, liver fat accumulation and/or elevated liver enzymes could be a good marker for impaired IS in both muscle and liver.

Recently the mesoderm-inducing effects of the transforming growth factor β (TGF-β) family of proteins have been widely examined. In an attemt to elucidate the functions of these proteins, porcine inhibin A and activin A (erythroid differentiation factor; EDF) were examined. Treatment of explants with activin A led to differentiation of mesodermal derivatives such as mesenchyme, notochord, blood cells and muscle, but inhibin A had a much lesser effect. The mesodermal differentiation induced by activin A was also comfirmed by analyses using a polyclonal antibody against muscle myosin. By indirect immunofluorescence analysis, the differentiation of muscle blocks was observed in the activin-A-treated explants, whereas no differentiation was observed in inhibin-A-treated and control explants. These findings confirm that this protein of the TGF-β family has mesoderm-inducing ability.