Effects of protoporphyrins on production of nitric oxide and expression of vascular endothelial growth factor in vascular smooth muscle cells and macrophages.

Heme oxygenase-1 (HO-1), an inducible enzyme degrading heme to biliverdin, iron and carbon monoxide, is involved in regulation of inflammation and angiogenesis. Tin protoporphyrin (SnPPIX) and zinc protoporphyrin (ZnPPIX) are commonly used as competitive inhibitors of HO-1. We aimed to compare the effects of SnPPIX and ZnPPIX on the production of vascular endothelial growth factor (VEGF), activity of inducible nitric oxide synthase (iNOS) and cell viability.

Carbon monoxide -- a "new" gaseous modulator of gene expression.

Carbon monoxide (CO) is an odorless, tasteless and colorless gas which is generated by heme oxygenase enzymes (HOs). HOs degrade heme releasing equimolar amounts of CO, iron and biliverdin, which is subsequently reduced to bilirubin. CO shares many properties with nitric oxide (NO), an established cellular messenger.

Delivery of high dose VEGF plasmid using fibrin carrier does not influence its angiogenic potency.

Delivery of DNA mixed with a degradable matrix carrier was supposed to improve transgene expression. Using a rabbit hind-limb ischemia model, we tested the angiogenic potency of plasmid encoding human vascular endothelial growth factor (pSG5-VEGF165) entrapped in fibrin sealant. Animals were injected intramuscularly with 500 microg of pSG5-VEGF165 or control plasmid, dissolved in saline (PBS) or fibrin glue.

Regulation of vascular endothelial growth factor synthesis by nitric oxide: facts and controversies.

Vascular endothelial growth factor (VEGF) is the major molecule governing angiogenesis, defined as the growth of blood vessels from vascular structure. There is abundant evidence that nitric oxide (NO) is an effector molecule mediating the activity of VEGF. By binding to its receptors, VEGF initiates the signaling cascades leading to NO production and angiogenic activation of endothelial cells.

HMG-CoA reductase inhibitors regulate inflammatory transcription factors in human endothelial and vascular smooth muscle cells.

Objective: Pleiotropic atheroprotective effects of HMG-CoA reductase inhibitors may be mediated on the level of vascular gene transcription. The aim of this study was to characterize the effects of statins on the activation of transcription factors known to regulate inflammation and cell proliferation/differentiation.

Methods And Results: Simvastatin, atorvastatin, and lovastatin (0.

Effect of prostaglandin-J(2) on VEGF synthesis depends on the induction of heme oxygenase-1.

Heme oxygenase-1 (HO-1) is an inducible enzyme that degrades heme to carbon monoxide, iron ions, and biliverdin. Its expression can be induced by 15-deoxy-Delta(12,14)prostaglandin-J(2) (15d-PGJ(2)), a natural ligand of peroxisome proliferator-activated receptor-gamma transcription factor. In macrophages and vascular smooth muscle cells, 15d-PGJ(2) up-regulates the expression of vascular endothelial growth factor (VEGF), a fundamental regulator of angiogenesis.

Vascular endothelial growth factor (VEGF) in ankylosing spondylitis--a pilot study.

Introduction: Angiogenesis is important for the pathogenesis of chronic inflammatory diseases in joints. Inflammation itself may upregulate the expression of VEGF in rheumatic diseases. Angiogenesis may become a new target for therapeutic intervention in inflammatory joint disease.

Atorvastatin decreases vascular endothelial growth factor in patients with coronary artery disease.

Objectives: The aim of this study was to test a possible influence of atorvastatin on the production of vascular endothelial growth factor (VEGF) in patients with coronary artery disease (CAD) and in vitro.

Background: Vascular endothelial growth factor is suggested to be involved in the growth of atherosclerotic plaque by inducing its neovascularization. Hepatic hydroxymethyl glutaryl-coenzyme A reductase inhibitors (statins) are known to have atheroprotective effects beyond lipid lowering.

Heme oxygenase activity modulates vascular endothelial growth factor synthesis in vascular smooth muscle cells.

Hypoxia, cytokines, and nitric oxide (NO) stimulate the generation of vascular endothelial growth factor (VEGF) and induce heme oxygenase-1 (HO-1) expression in vascular tissue. HO-1 degrades heme to carbon monoxide (CO), iron, and biliverdin, the latter being reduced to bilirubin by biliverdin reductase. In the present study, we investigated the role of HO-1 in the modulation of VEGF synthesis in rat vascular smooth muscle cells (VSMC).

Ligands of peroxisome proliferator-activated receptor-gamma increase the generation of vascular endothelial growth factor in vascular smooth muscle cells and in macrophages.

Peroxisome proliferator-activated receptors-gamma (PPARgamma) are ligand-inducible transcription factors of the nuclear hormone receptor superfamily. We examined the effect of PPARgamma activation on the generation of vascular endothelial growth factor (VEGF), one of the major angiogenic agents. Rat vascular smooth muscle cells (VSMC) and murine macrophages RAW264.

Mean free path and peak dispersion in the geometration motion in gel electrophoresis.

The concept of the mean free path, i.e., the mean distance between subsequent collisions of DNA molecules with gel fibers, is introduced to the model description of the geometration effect.

Vascular endothelial growth factor synthesis in vascular smooth muscle cells is enhanced by 7-ketocholesterol and lysophosphatidylcholine independently of their effect on nitric oxide generation.

Nitric oxide (NO) generated by inducible NO synthase (iNOS) enhances vascular endothelial growth factor (VEGF) synthesis in vascular smooth muscle cells (VSMC) and both NO and modified low density lipoprotein (LDL) augment VEGF production in macrophages. Oxidized LDL (oxLDL) are known inhibitors of NO generation in the cells of vascular wall. As the relationship between VEGF, iNOS and oxLDL has not been well elucidated, we studied the effect of two main components of oxLDL, 7-ketocholesterol (7-Kchol) and lysophosphatidylcholine (LPC), on VEGF and NO synthesis in rat VSMC and on VEGF synthesis in human VSMC.

Prostaglandin-J2 induces synthesis of interleukin-8 by endothelial cells in a PPAR-gamma-independent manner.

PPARgamma is a transcription factor of nuclear receptor superfamily, involved in the regulation of inflammation. We investigated the influence of PPARgamma-ligands, 15-deoxy-delta12,14 prostaglandin-J2 (15d-PGJ2), and ciglitazone, on the generation of interleukin-8 (IL-8) by the human microvascular endothelial cell line (HMEC- 1). Expression of PPARgamma in HMEC-1 was confirmed by RT-PCR.

Genetic augmentation of nitric oxide synthase increases the vascular generation of VEGF.

Objective: Vascular endothelial growth factor (VEGF) induces the release of nitric oxide (NO) from endothelial cells. There is also limited data suggesting that NO may enhance VEGF generation.

Methods: To further investigate this interaction, we examined the effect of exogenous and endogenous NO on the synthesis of VEGF by rat and human vascular smooth muscle cells (VSMC) by exposing cells to exogenous NO donors, or to genetic augmentation of eNOS or iNOS.

Vascular endothelial growth factor is efficiently synthesized in spite of low transfection efficiency of pSG5VEGF plasmids in vascular smooth muscle cells.

The limitation of lipotransfection with plasmid vectors is its low efficiency and the short-term expression of introduced genes. This is particularly important when the synthesis of high amounts of therapeutic products is required. However, growth factors with paracrine action overcome this problem.

Nitric oxide induces the synthesis of vascular endothelial growth factor by rat vascular smooth muscle cells.

Vascular endothelial growth factor (VEGF) is known to induce the release of nitric oxide (NO) from endothelial cells. However, the effect of NO on VEGF synthesis is not clear. Accordingly, the effect of endogenous and exogenous NO on VEGF synthesis by rat vascular smooth muscle cells (VSMCs) was investigated.

Nitric oxide mediates the mitogenic effects of insulin and vascular endothelial growth factor but not of leptin in endothelial cells.

The regulation of vascular wall homeostasis by nitric oxide (NO) generated by endothelium is being intensively studied. In the present paper, the involvement of NO in the vascular endothelial growth factor (VEGF), insulin or leptin-stimulated proliferation of human endothelial cells (HUVEC) was measured by [3H]thymidine or bromodeoxyuridine incorporation. VEGF and insulin, but not leptin, increased NO generation in HUVEC, as detected with ISO-NO electrode.

Gene transfer of vascular endothelial growth factor and endothelial nitric oxide synthase--implications for gene therapy in cardiovascular diseases.

Gene therapy is based on the delivery of exogenous genetic material in order to influence the endogenous genetic components involved in disease development. This new therapeutic approach has been suggested to have great potential in the treatment of insufficient angiogenesis or in prevention of restenosis after balloon angioplasty of atherosclerotic arteries. As both vascular endothelial growth factor (VEGF) and nitric oxide (NO) exert beneficial effects on vascular physiology, we studied the generation of both compounds after in vitro transfection of relevant genes.

Oxidized low density lipoprotein inhibits inducible nitric oxide synthase, GTP cyclohydrolase I and transforming growth factor beta gene expression in rat macrophages.

Several studies have already demonstrated that oxidized- LDL decreases nitric oxide (NO) generation by cytokine-stimulated macrophages. However, the mechanisms of such an inhibition have not been yet elucidated. NO generation by inducible nitric oxide synthase (iNOS) is dependent on the presence of cofactors for NO generation, tetrathydrobiopterin (BH4) among them.

Expression of beta-galactosidase gene and endothelial nitric oxide synthase gene in rat vascular smooth muscle cells after in vitro lipotransfection.

The aim of this study was to optimize the conditions for in vitro lipotransfection of rat vascular smooth muscle cells (VSMC) with bacterial beta-galactosidase gene and bovine endothelial nitric oxide synthase (ecNOS) gene. Transfection efficiency of four liposomes: Transfectam, Lipofectin, Unifectin-10, and Maxifectin was compared. The best results (efficiency 1-5%) were obtained with Maxifectin, when transfections were performed in VSMC cultures being at 50% confluency, with 1 microg DNA and 10 microl liposome per well, and when the liposome/DNA complexes were coincubated with the cells for 24 h.

Gene transfer of nitric oxide synthase: effects on endothelial biology.

Objectives: The purpose of the study was to investigate the role of nitric oxide (NO) in monocyte-endothelial interaction by augmenting NO release via transfection of human endothelial cells (ECs) with EC NO synthase (eNOS) DNA.

Background: Enhancement of NO synthesis by L-arginine or shear stress reduces endothelial adhesiveness for monocytes and inhibits atherogenesis. To elucidate further the underlying mechanism, we augmented NO synthase expression by transfection of human EC.

[Molecular basis of chronic myelogenous leukemia and significance of diagnostic methods based on BCR-ABL gene amplification].

Chronic myelogenous leukemia is characterized by an abnormal 22nd chromosome known as a Philadelphia chromosome, which can be detected in 95% of patients with CML. Molecular equivalent of this aberration is a BCR-ABL translocation resulting in chimeric gene formation. A BCR-ABL chimeric gene plays a key role in the hematopoietic cells proliferation regulation.