Vascular endothelial growth factor (VEGF) stimulated a time‐ and concentration‐dependent increase in PGI 2 synthesis human umbilical vein cells with mean maximum of 2‐fold above basal levels at 25 ng/ml after 60 min. VEGF also rapidly the release arachidonic acid phosphorylation activation cytosolic phospholipase A (cPLA ). The VEGF‐related factor, placenta (PlGF), had little effect on synthesis, or cPLA activation. PD98059, selective inhibitor MAP kinase kinase, caused complete inhibition...

Hyperammonemia is a feature of liver failure, which associated with increased risk infection. The aims the present study were to determine in vitro, rats fed an ammoniagenic diet and patients cirrhosis, whether induction hyperammonemia results neutrophil dysfunction. As produces cell swelling, we explored role osmoregulating, p38 mitogen-activated protein kinase (p38(MAPK)) pathway mediating this Neutrophils isolated from blood healthy volunteers incubated either 75 microM ammonia or...

Abstract Communication between endothelial and bone cells is crucial for controlling vascular supply during growth, remodeling, repair but the molecular mechanisms coordinating this intercellular crosstalk remain ill‐defined. We have used primary human rat long bone‐derived osteoblast‐like (HOB LOB) umbilical vein (HUVEC) to interrogate potential autocrine/paracrine role of cell growth factor (VEGF) in osteoblast:endothelial (OB:EC) communication examined whether prostaglandins (PG), known...

ABSTRACT Adenosine is released from the myocardium, endothelial cells, and skeletal muscle in ischemia an important regulator of coronary blood flow. We have already shown that acute (2 min) activation A 2a purinoceptors stimulates NO production human fetal umbilical vein cells (1) now report a key role for p42/p44 mitogen‐activated protein kinases (p42/p44 MAPK ) regulation L‐arginine‐nitric oxide (NO) signaling pathway. Expression mRNA ‐, 2b 3 ‐adenosine receptor subtypes was abundant...

Background The adipocyte-derived hormone leptin influences the behaviour of a wide range cell types and is now recognised as pro-angiogenic pro-inflammatory factor. In vasculature, these effects are mediated in part through its direct receptor (ObRb)-driven actions on endothelial cells (ECs) but mechanisms responsible for activities have not been established. this study we sought to more fully define molecular links between inflammatory angiogenic responses leptin-stimulated human ECs....

Obesity and saturated fatty acid (SFA) treatment are both associated with skeletal muscle insulin resistance (IR) increased macrophage infiltration. However, the relative effects of SFA unsaturated (UFA)-activated macrophages on unknown. Here, were treated palmitic acid, palmitoleic or conditioned medium (CM) C2C12 myotubes investigated. CM from acid-treated J774s (palm-mac-CM) impaired signalling insulin-stimulated glycogen synthesis, reduced Inhibitor κBα phosphorylation p38...

Abstract Bone cells' early responses to estrogen and mechanical strain were investigated in the ROS 17/2.8 cell line. Immunoblotting with antiphosphorylated receptor α (ER-α) antibody showed that when these cells exposed for 10 minutes (10−8 M) or a single period of cyclic dynamic (peak 3400 μϵ, 1Hz, 600 cycles), there was an increase intensity 66-kDa band, indicating phosphorylation ser122 amino terminus ER-α. Increased detected within 5 exposure after end strain. Estrogen also activated...

The functional significance of protease-activated receptors (PARs) in endothelial cells is largely undefined, and the intracellular consequences their activation are poorly understood. Here, we show that serine protease thrombin, a PAR-1-selective peptide (TFLLRN), SLIGKV (PAR-2-selective peptide) induce cyclooxygenase-2 (COX-2) protein mRNA expression human without modifying COX-1 expression. COX-2 induction was accompanied by sustained production 6-keto-PGF1alpha, stable hydrolysis product...

Arterial medial calcification (AMC) is the deposition of calcium phosphate mineral, often as hydroxyapatite, in layer arteries. AMC shares some similarities to skeletal mineralisation and has been associated with transdifferentiation vascular smooth muscle cells (VSMCs) towards an osteoblast-like phenotype. This study used primary mouse VSMCs calvarial osteoblasts directly compare established widely vitro models bone formation. Significant differences were identified between calcifying...

Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors used worldwide to manage dyslipidaemia and thus limit the development of atherosclerotic disease its complications. These atheroprotective drugs now known exert pleiotropic actions outside their cholesterol-lowering activity, including altering immune cell function. Macrophages phagocytic leukocytes that play critical functional roles in pathogenesis atherosclerosis directly targeted by statins. Early studies...

We reported previously that vascular endothelial growth factor (VEGF) stimulates prostacyclin (PGI(2)) production via activation of the extracellular signal-regulated kinase (ERK) cascade. In this paper, we examined role protein C (PKC) in pathway. VEGF-induced PGI(2) generation and arachidonic acid release human umbilical vein cells were inhibited by PKC inhibitors GF109203X calphostin C. VEGF increased activity immunoreactivity PKCdelta, alpha epsilon isoforms particulate fractions cells....

Up-regulation of proteinase-activated receptor-2 (PAR2) is a factor in number disease states and we have therefore examined the signalling pathways involved expression receptor.

Although concern remains about the athero-thrombotic risk posed by cyclo-oxygenase (COX)-2-selective inhibitors, recent data implicates rofecoxib, while celecoxib appears equivalent to NSAIDs naproxen and ibuprofen. We investigated hypothesis that activates AMP kinase (AMPK) signalling enhance vascular endothelial protection. In human arterial venous cells (EC), in contrast ibuprofen naproxen, induced protective protein heme oxygenase-1 (HO-1). Celecoxib derivative 2,5-dimethyl-celecoxib...

Arterial medial calcification (AMC) is thought to share some outward similarities skeletal mineralization and has been associated with the transdifferentiation of vascular smooth muscle cells (VSMCs) an osteoblast‐like phenotype. ATP UTP have previously shown inhibit bone mineralization. This investigation compared effects extracellular nucleotides on in VSMCs those seen osteoblasts. ATP, ubiquitous inhibitor, pyrophosphate (PP i ), dose dependently inhibited VSMC by ≤85%. Culture calcifying...

This study was conducted to determine whether the ERK1/2 family of MAPKs can be modulated by physiological regulators human corpus luteum, and this activation is important for progesterone secretion in granulosa-lutein (hGL) cells. Human LH (hLH), hCG, agents that indirectly elevate cAMP [cholera toxin, forskolin, (Bu)(2)cAMP], time- dose-dependently activated hGL reduced preincubation with PKA inhibitors, including myristoylated PKI, suggesting mediates activation. Two structurally distinct...

It is well established that local modification of extracellular matrix (ECM) hyaluronan composition vital in the regulation cell behavior. Indeed, formation articulating chick joint cavities, which requires mechanical stimuli derived from skeletal movement, dependent upon accumulation an ECM rich (HA). However, mechanisms responsible for such precise mechano-dependent behavior and a HA-rich remain undefined. Here we show extracellular-regulated kinase 1/2 (ERK1/2) selectively activated cells...