Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009443 (cold)
 92,137 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of vascular endothelial growth factor (VEGF) in blood-brain barrier (BBB) breakdown and angiogenesis, observed previously in the cerebral cortical cold-injury model, was investigated. Immunohistochemistry was used to assess BBB permeability to plasma fibronectin and to localize VEGF protein in the cortical cold-injury model over a period of 10 min to 14 days post-injury. BBB breakdown to fibronectin in lesion vessels was observed at 10 min post-injury, was maximal between 2 and 4 days and declined gradually thereafter, while occasional perilesional vessels remained permeable up to 6 days. Increased VEGF immunoreactivtiy occurred later-it was observed in pial vessels after 6 hours (h), and persisted up to day 14. Arterioles within the cold lesion showed VEGF immunoreactivity at 36 h, thus preceding the onset of endothelial proliferation and angiogenesis that occurred from day 3 to day 5. VEGF immunoreactivity was also observed in inflammatory cells and astrocytes. These results indicate that the immediate breakdown of the BBB in the cold lesion is unrelated to VEGF. The presence of mural VEGF in permeable pial vessels and lesional arterioles suggests that VEGF is one of several factors that mediates BBB breakdown in this model. The association of maximal VEGF immunoreactivity with endothelial proliferation and neovascularization suggests that VEGF promotes angiogenesis and repair following brain trauma.
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PMID:Role of vascular endothelial growth factor in blood-brain barrier breakdown and angiogenesis in brain trauma. 925 61

Human immunodeficiency virus-1 (HIV-1) Tat protein can be released by infected cells and activates mesenchymal cells. Among these, monocytes respond to Tat by migrating into tissues and releasing inflammatory mediators. In the present study, we have examined the molecular mechanism of monocyte activation by Tat, showing that this viral protein signals inside the cells through the tyrosine kinase receptor for vascular endothelial growth factor encoded by fms-like tyrosine kinase gene (VEGFR-1/Flt-1). Subnanomolar concentrations of Tat induced monocyte chemotaxis, which was inhibited by cell preincubation with vascular-endothelial growth factor-A (VEGF-A). This desensitisation was specific for VEGF-A, because it not was observed with FMLP. In addition, the soluble form of VEGFR-1 specifically inhibited polarization and migration induced by Tat and VEGF-A, thus confirming the common use of this receptor. Binding studies performed at equilibrium by using radiolabeled Tat showed that monocytes expressed a unique class of binding site, with a kd of approximately 0.2 nmol/L. The binding of radiolabeled Tat to monocyte surface and the cross-linking to a protein of 150 kD was inhibited specifically by an excess of cold Tat or VEGF-A. Western blot analysis with an antibody anti-VEGFR-1/Flt-1 performed on monocyte phosphoproteins immunoprecipitated by an monoclonal antibody anti-phosphotyrosine showed that Tat induced a rapid phosphorylation in tyrosine residue of the 150-kD VEGFR-1/Flt-1. Taken together, these results suggest that biologic activities of HIV-1 Tat in human monocytes may, at least in part, be elicited by activation of VEGFR-1/Flt-1.
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PMID:Tat-human immunodeficiency virus-1 induces human monocyte chemotaxis by activation of vascular endothelial growth factor receptor-1. 926 52

The thermogenic activity of brown adipose tissue (BAT) is heavily dependent on high perfusion, through its dense vascular system. Angiogenesis must go hand-in-hand with BAT functions, but little is known about the factors controlling it. In the present study we demonstrate that: (a) vascular endothelial growth factor (VEGF) is synthesised and released in brown adipocytes in culture; (b) VEGF mRNA isoforms and protein appear in dispersed mature brown adipocytes and whole tissue; (c) VEGF expression is increased in BAT from cold-exposed rats, and in cultured brown adipocytes exposed to noradrenaline and the beta3-adrenoceptor agonists; (e) BAT from genetically obese (falfa) rats exhibits reduced expression of VEGF as well as a change in the ratio of mRNA isoforms. It is concluded that sympathetic control of VEGF expression via noradrenaline acting on beta3-adrenoceptors plays a major role in developmental and adaptive angiogenesis, and defects in this contribute to the reduced thermogenic capacity of BAT in genetic obesity.
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PMID:Role of sympathetic activity in controlling the expression of vascular endothelial growth factor in brown fat cells of lean and genetically obese rats. 992 95

Brown adipose tissue (BAT) is the major site of non-shivering thermogenesis in rodents. Rapid angiogenesis is induced in association with adaptive hyperplasia of this tissue when the animal is exposed to cold. We demonstrated previously adrenergic activation of mRNA expression of vascular endothelial growth factor (VEGF) in rat BAT and its possible contribution to the cold-induced angiogenesis in this tissue. In the present study, we examined the effect of cold exposure on mRNA expression of other two angiogenic factors, VEGF-B and basic fibroblast growth factor (bFGF), in rats. Conventional Northern blot analysis revealed abundant mRNA expression of VEGF-B as well as VEGF, but not bFGF, in BAT. When rats were exposed to cold at 4 degrees C, the VEGF mRNA level was increased by 2.7-fold in 1-4 hr and returned to the basal level within 24 hr. In contrast, the VEGF-B mRNA level did not change throughout the course of cold exposure. A significant expression of bFGF mRNA was detected in BAT by reverse transcription-polymerase chain reaction (RT-PCR). To evaluate the tissue bFGF mRNA level quantitatively, a competitive RT-PCR method was developed using a shorter RNA fragment as a competitor. The bFGF mRNA level in BAT was found to increase by 2.3-fold in 4 hr and decreased to the basal level within 24 hr after cold exposure. These results suggest that cold exposure leads to induce VEGF and bFGF rapidly and transiently in BAT, which in turn stimulate the proliferation of vascular endothelial cells in this tissue.
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PMID:Cold-induced mRNA expression of angiogenic factors in rat brown adipose tissue. 1034 92

The critical role of skeletal muscle capillaries is the supply of oxygen to skeletal muscle fibers during conditions of maximal aerobic work. The supply of substrates under these conditions is not limited by the vascular bed but rather by the capacity of the sarcolemmal transporter systems. Because of this dominant role of oxygen supply in muscle tissue, hypoxia has generally been considered to be an important stimulus for capillary neo-formation in skeletal muscle. Early morphometric work seemed to indicate that animals exposed to permanent hypoxia had in fact a significantly improved vascular supply in muscle tissue. Later work questioned these early findings and it was concluded that hypoxia per se was not a sufficient stimulus for capillary neo-formation but that additional stimuli such as cold-exposure needed to be present. In humans exposed to severe hypoxia during simulated or real ascents to Mt. Everest an increase in capillary density was in fact found. However, this increase could be shown to result from a reduction of muscle fiber volume and not from capillary growth. Broadly compatible results were obtained in animal experiments in which changes in capillarity were assessed in muscles with limited blood supply which were exposed to chronic electrical stimulation. Recently we have shown that endurance exercise training in humans results in a rise in mRNA of vascular endothelial growth factor (VEGF) only when carried out vigorously and in hypoxia. These results indicate that molecular techniques will allow in the near future to delineate the role played by hypoxia in capillary neo-formation.
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PMID:Vascular growth in hypoxic skeletal muscle. 1063 7

Vasoactive and angiogenic factors are involved in the autocrine/paracrine thyroid regulation of microvascular bed during goiter development. In the thyroid of old mice, the presence of slowly functioning ('cold') follicles allowed us to study the microvascular regulation of each follicle in correlation with the immunohistochemical expression of vascular endothelial growth factor (VEGF) and nitric oxide synthase III (NOSIII). Mice aged 20 months did or did not receive a goitrogenic treatment (low iodine diet and propylthiouracyl), and their thyroids were processed for light and electron microscopy, and for autoradiography. The relative volumes (Vv) of the capillaries, the number of vessels per follicular area, the mean capillary area and the number of [(3)H]thymidine labeled nuclei were measured separately for 'hot' and 'cold' follicles. Already in control mice, the capillary bed surrounding 'hot' follicles was significantly larger than that seen around 'cold' follicles, because of larger diameters and twice the number of capillaries. This difference persisted whatever the length of the stimulatory treatment. During this treatment, the Vv of the capillaries increased to a larger extent around 'hot' follicles than around 'cold' ones. All vascular changes around 'cold' follicles were less extended and the increase in the capillary diameter was delayed. In control mice, the 'cold' follicles were negative for NOSIII and positive for VEGF while 'hot' follicles were positive for both. During stimulation, all follicles became progressively NOSIII positive. These data support the concept of 'angio-follicular units' in the thyroid and demonstrate their differential regulation in chronic stimulation during which local secretion of VEGF and NO is clearly involved.
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PMID:Evidence for co-ordinated changes between vascular endothelial growth factor and nitric oxide synthase III immunoreactivity, the functional status of the thyroid follicles, and the microvascular bed during chronic stimulation by low iodine and propylthiouracyl in old mice. 1082 30

Stress responses induced in fibroblasts by cryopreservation were compared in suspension or three-dimensional cultures at various times up to 5 days of recovery. Cryopreservation caused an 86% inhibition in [(35)S]methionine incorporation, with recovery over 2 days to 45% &plusmn: 14% of its original value. Stress proteins, including heat shock protein (hsp) and glucose-regulated proteins (GRP), detected by immunoblotting, responded with transient increases in cellular content (hsp27 and hsp90 in suspension and three-dimensional culture, and hsp70 only in three-dimensional culture), decreases at 24 h (hsp56, hsp70, hsp90, and GRP78 in three-dimensional culture and hsp90 in suspension), or little change (hsp70 in suspension). Polyacrylamide gel electrophoresis of [(35)S]methionine-labeled proteins showed transient induction of hsp47 within 4 h, and increased synthesis of hsp90 and GRP78 and other unidentified proteins at 24 h, but no change in hsp70. The mitogen-activated protein (MAP) kinase, p38, showed a transient increase after thawing, followed by a peak in extracellular signal-regulated kinase at 24 h. The stress-activated protein kinase (JNK) was not activated. In both stress protein and MAP kinase responses, the three-dimensional cultures showed a more intense response than fibroblasts in suspension. Although some responses were related to osmotic and cold stress during freezing, others were unique. Cryopreservation induced mRNA for selected growth factors, including vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) A chain, which increased 5- to 20- fold at 48 h returning to basal levels by 120 h. Our results indicate the novel finding that cryopreservation of fibroblasts grown in three-dimensional culture induced a specific cellular stress response including growth factors.
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PMID:Comparison of the stress response to cryopreservation in monolayer and three-dimensional human fibroblast cultures: stress proteins, MAP kinases, and growth factor gene expression. 1107 40

We have shown that brown adipose tissue (BAT), a thermogenic organ in mammals, expresses high levels of vascular endothelial growth factor (VEGF) mRNA in response to exposure to cold, which may contribute to angiogenesis associated with cold-induced hyperplasia of this tissue. In the present study, we examined mRNA expression of not only VEGF, but also VEGF-B and VEGF-C, recently cloned VEGF isoforms, in vitro using immortal brown adipocytes (HB2) isolated from mouse BAT. HB2 preadipocytes expressed detectable levels of VEGF, VEGF-B and VEGF-C mRNA, but a low level of VEGF. After HB2 cells differentiated into adipocytes, the VEGF mRNA level increased without a noticeable change in the VEGF-B and VEGF-C mRNA levels. When HB2 cells were stimulated by norepinephrine, the VEGF mRNA level increased without a change in that of VEGF-B, while the VEGF-C mRNA level decreased. A marked reduction of VEGF-C mRNA expression was also found when HB2 cells were treated with agonists of peroxisome proliferator-activated receptor gamma (PPARgamma, troglitazone), retinoic acid receptor (RAR, all-trans retinoic acid) and retinoid X receptor (RXR, 9-cis retinoic acid). These results suggest a specific adrenergic mechanism for up-regulation of VEGF expression different from those for other VEGF isoforms, and thereby the major contribution of VEGF to the cold-induced angiogenesis in BAT. In addition, the agonists of PPARgamma, RAR and RXR are suggested to be inhibitory to angiogenesis through the reduction of VEGF-C production.
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PMID:Isoform-specific regulation of vascular endothelial growth factor (VEGF) family mRNA expression in cultured mouse brown adipocytes. 1130 73

Our previous study demonstrated that vascular endothelial growth factor (VEGF), now referred to as VEGF-A, plays a significant role in blood-brain barrier (BBB) breakdown and angiogenesis after brain injury. In this study, VEGF-A expression was compared with that of VEGF-B in the rat cortical cold injury model over a period of 6 hours to 6 days post-injury. VEGF-A and VEGF-B mRNA were detected by in situ hybridization and their protein was detected by immunohistochemistry. The presence of VEGF-A and VEGF-B proteins in endothelium of lesion vessels was related to BBB breakdown by double labeling for either of these growth factors and fibronectin, which was used as a marker of BBB breakdown. Significant induction of both VEGF-A and VEGF-B mRNA occurred at the lesion site during the period of maximal endothelial proliferation. VEGF-A mRNA levels peaked at 3 and 4 days post-injury and returned to basal expression by day 6, while VEGF-B mRNA levels remained elevated up to day 6. VEGF-B protein was constitutively expressed in endothelium of all cerebral vessels. After brain injury, there was increased immunoreactivity for VEGF-B at the lesion site, this protein being present in the endothelium and vascular smooth muscle cells of pial vessels, in inflammatory cells, and later in proliferating endothelial cells, endothelium of neovessels, and astrocytes. Lesion vessels showing BBB breakdown to fibronectin showed endothelial VEGF-A protein but not VEGF-B protein. Constitutive expression of VEGF-B in normal endothelium suggests that it may have a role in maintenance of the BBB in steady states, while its induction at both the gene and protein level post-injury indicates that it has an essential role in angiogenesis and the repair processes after brain injury.
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PMID:Differential expression of vascular endothelial growth factor-A (VEGF-A) and VEGF-B after brain injury. 1223 Mar 24

Overexpression of vascular endothelial growth factor (VEGF) is implicated in a number of diseases. It is therefore critical that mechanisms exist to strictly regulate VEGF expression. A hypoxia-responsive (HR) region of the VEGF promoter which binds the HIF-1 transcription factor is a target for many signals that up-regulate VEGF transcription. Repressors targeting the HIF-1 transcription factor have been identified but no repressors directly binding the HR promoter region had been reported. We now report a novel mechanism of repression of the VEGF HR region involving DNA binding. We find that single strand DNA-specific cold shock domain (CSD or Y-box) proteins repress the HR region via a binding site downstream of the HIF-1 site. The repressor site is functional in unstimulated, normoxic fibroblasts and represents a novel means to prevent expression of VEGF in the absence of appropriate stimuli. We characterized complexes forming on the VEGF repressor site and identified a previously unreported nuclear CSD protein complex containing dbpA. Nuclear dbpA appears to bind as a dimer and we determined a means by which nuclear CSD proteins may enter double strand DNA to bind to their single strand sites to bring about repression of the VEGF HR region.
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PMID:A novel mechanism of repression of the vascular endothelial growth factor promoter, by single strand DNA binding cold shock domain (Y-box) proteins in normoxic fibroblasts. 1243 87


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