1,720,997 research outputs found
Protein kinase C pathway and proliferative response of aged and young rat vascular smooth muscle cell.
No full textEffects of toll-like receptor-4 gene polymorphisms on soluble P-selectin and von Willebrand factor levels in hypercholesterolemic patients.
No full textCirculating leptin is associated with oxidized LDL in postmenopausal women.
No full textRecently, leptin has been suggested as a possible cause of atherosclerotic disease. In the present study,we have investigated in postmenopausal women (n = 60; age: 52 ± 13) the relationship between circulating levels of leptin, oxidized LDL (Ox-LDL) and other biochemical and anthropometric variables of atherosclerotic risk. In addition, we have evaluated soluble thrombomodulin (sTM) as a marker of endothelial damage. An additional study was conducted in a subgroup of obese subjects to determine the short-term effects of weight loss on selected variables. Ox-LDL showed a positive correlation with leptin circulating levels (r = 0.65, P < 0.0001). A significant association was also found between Ox-LDL and body mass index (r = 0.69, P < 0.0001), waist-to-hip ratio (r = 0.50, P < 0.0001), insulin levels (r = 0.65, P < 0.0001), HOMA index (r = 0.55, P < 0.0001) and sTM (r = 0.74, P < 0.0001) levels. After multivariate regression analysis leptin was still related to Ox-LDL levels (P = 0.007). In obese women who completed the program of weight reduction, leptin changes persisted as a significant predictor of plasma changes in Ox-LDL levels. These findings suggested a novel link between leptin and Ox-LDL, possibly involved in atherosclerotic disease
Soluble thrombomodulin and vascular adhesion molecule-1 are associated to leptin plasma levels in obese patients.
No full textStatins have been shown to interact with several monocyte/macrophage functions. We tested the effect of pravastatin on transforming growth factor-β1 (TGF-β1) production and its possible involvement in scavenger receptors class A (SRA) expression in human THP-1 cells. TGF-β1s biological activity in THP-1 cell conditioned medium, evaluated by luciferase activity of transfected cell with a TGF-β responsive promoter, was increased in a dose-dependent manner after incubation with pravastatin (1-20μM). Pravastatin (1-20μM) induced a dose-dependent increase in TGF-β1 mRNA expression and protein production in THP-1 cells. PMA-induced SRA gene and protein expression was suppressed by pravastatin with a mean 3-fold decrease at 10μM. This last effect was reversed by a mouse monoclonal anti-TGF-β1 neutralizing antibody. PD98059, a specific inhibitor of MAP kinase cascade, completely reversed pravastatin-induced SRA down-regulation. p44 and p42 isoforms showed a dose-dependent phosphorylation after treatment with pravastatin (1-20μM) which was inhibited by a mouse monoclonal anti-TGF-β1 antibody. Our results demonstrate that pravastatin significantly up-regulates TGF-β1 expression which may be in involved in down-regulation of SRA expression in THP-1 cell cultures. A new pathway for pravastatin effects in atherogenesis can be suggested. © 2003 Elsevier Inc. All rights reserved
Effect of interleukin-1 receptor antagonist (IL-1RA) on vascular smooth muscle cell proliferation (VSMC).
No full textModulation of rat vascular smooth muscle cell (VSMC) proliferation by cysteinyl leukotriene D4: a role for mediation of interleukin 1
No full textCholesterol feeding modulates type 1 and type II TGF-beta receptor expression and fibrogenic vascular remodeling in C57BL/6 mice.
No full textLow arginine intake reduces levels of solubile P-selectin in hypercholesterolemic patients.
No full textDifferences in the glutathione system of cultured aortic smooth muscle cells from young and aged rats: effect of DL-Buthionine-SR-Sulphoxime.
No full textModulatory effects of heparin on cellular accumulation and cytotoxicity of doxorubicin in MRP1-overexpressing HL60/doxo cells.
No full textBACKGROUND: The overexpression of multidrug resistance protein (MRP1), associated with high levels of intracellular glutathione (GSH), is a well characterized mechanism of multidrug resistance (MDR) in several malignancies. Various chemosensitizers have been used in vitro to modulate the MRP1 activity, but the high toxicity limits their clinical application. Unfractionated heparin (UFH), is frequently used to prevent thrombo-embolic complications in cancer patients. This in vitro study aimed to elucidate the potential role of UFH as a sensitizer in anticancer clinical chemotherapy.
MATERIALS AND METHODS: The human leukemic doxorubicin-resistant cell line (HL60/doxo), which overexpresses the MRP1 protein was treated with UFH alone or in combination with three different concentrations of doxo. The intracellular accumulation and cytotoxicity of doxo and the cellular GSH content were measured in comparison with the leukotriene LTD4 receptor antagonist, MK571, a specific MRP1 inhibitor.
RESULTS: UFH increased doxo accumulation and cytotoxicity in the HL60/doxo cell line with respect to cells treated with doxo alone. UFH also decreased the cellular GSH content in the HL60/doxo cells with respect to the control, suggesting a potential involvement of UFH in doxo co-transport with GSH.
CONCLUSION: Our results demonstrate that UFH modulates MRP1-mediated MDR in HL60/doxo cells expressing high MRP1 levels. These findings suggest a potential clinical application of heparin as an adjuvant to overcome MRP1-mediated drug resistance in cancer patients
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