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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have noted that n-3 fatty acid-rich oils, such as fish oil, perilla oil and flaxseed oil as well as ethyl docosahexaenoate (DHA) prolonged the survival time of stroke-prone spontaneously hypertensive rats (SHRSP) rats by approximately 10% as compared with linoleate (n-6)-rich safflower oil. Rapeseed oil with a relatively low n-6/n-3 ratio unusually shortened the survival time by approximately 40%, suggesting the presence of minor components unfavorable to SHRSP rats. This study examined the effects of dietary oils and DHA on renal injury and gene expression related to renal injury in SHRSP rats. Rats fed rapeseed oil- and safflower oil-supplemented diets developed more severe proteinuria than those fed soybean oil-supplemented diet used as a control, but there were no significant differences in blood pressure. In contrast, the DHA-supplemented diet inhibited the development of proteinuria and suppressed hypertension. The mRNA levels for renal TGF-beta, fibronectin and renin were higher in the rapeseed oil and safflower oil groups after 9 weeks of feeding of the experimental diet than in the soybean oil and DHA groups. The fatty acid composition of kidney phospholipids was markedly affected by these diets. These results indicate that the renal injury observed in the groups fed safflower oil with a high n-6/n-3 ratio and rapeseed oil with presumed minor components is accompanied by increased expression of the TGF-beta, renin and fibronectin genes, and that dietary DHA suppresses renal injury and gene expression as compared with soybean oil.
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PMID:Dietary docosahexaenoic acid ameliorates, but rapeseed oil and safflower oil accelerate renal injury in stroke-prone spontaneously hypertensive rats as compared with soybean oil, which is associated with expression for renal transforming growth factor-beta, fibronectin and renin. 1060 99

Hypertension, a remediable risk factor for stroke, cardiovascular disease, and renal failure, affects 50 million individuals in the United States alone. African Americans (blacks) have a higher incidence and prevalence of hypertension and hypertension-associated target organ damage compared with Caucasian Americans (whites). Herein, we explored the hypotheses that transforming growth factor-beta(1) (TGF-beta(1)) is hyperexpressed in hypertensives compared with normotensives and that TGF-beta(1) overexpression is more frequent in blacks compared with whites. These hypotheses were stimulated by our recent demonstration that TGF-beta(1) is hyperexpressed in blacks with end-stage renal disease compared with white end-stage renal disease patients and by the biological attributes of TGF-beta(1), which include induction of endothelin-1 expression, stimulation of renin release, and promotion of vascular and renal disease when TGF-beta(1) is produced in excess. TGF-beta(1) profiles were determined in black and white hypertensive subjects and normotensive controls and included circulating protein concentrations, mRNA steady-state levels, and codon 10 genotype. Our investigation demonstrated that TGF-beta(1) protein levels are highest in black hypertensives, and TGF-beta(1) protein as well as TGF-beta(1) mRNA levels are higher in hypertensives compared with normotensives. The proline allele at codon 10 (Pro(10)) was more frequent in blacks compared with whites, and its presence was associated with higher levels of TGF-beta(1) mRNA and protein. Our findings support the idea that TGF-beta(1) hyperexpression is a risk factor for hypertension and hypertensive complications and provides a mechanism for the excess burden of hypertension in blacks.
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PMID:Transforming growth factor-beta 1 hyperexpression in African-American hypertensives: A novel mediator of hypertension and/or target organ damage. 1072 60

In isolated cardiomyocytes, hypertrophic responsiveness to beta-adrenergic stimulation can be induced by pre-exposure of the cells to TGF-beta. To characterize genes involved in beta-adrenergically mediated hypertrophy, mRNA expression patterns in isoprenaline-stimulated cardiomyocytes which were pre-exposed to TGF-beta were analysed by differential display RT-PCR analysis. Eighteen fragments, upregulated by isoprenaline, were identified. Six of them, which code for proteins with known function, were further analysed by RT-PCR (1) to verify their induction after beta-adrenergic stimulation, (2) to restrict their number to genes only upregulated after hypertrophy inducing beta-adrenergic stimulation, and (3) to study their expression in stroke-prone spontaneous hypertrophic rats (SHR-sp), an in vivo model of myocardial hypertrophy, in which elevated levels of TGF-beta are found. Induction by isoprenaline could be proved for all but one of the six genes. Further analysis of these genes in freshly isolated myocytes, which respond with hypertrophic growth only to alpha--but not beta--adrenergic stimulation, revealed that three of them, coding for the translation initiation factor sui 1, the cis-golgi transport protein p28 and the mitochondrial NADH-dehydrogenase II subunit, are specifically induced in TGF-beta-pre-exposed cardiomyocytes after beta-adrenergic stimulation. Their induction is therefore closely associated with a beta-adrenergic growth response in isolated cardiomyocytes. p28-mRNA is also markedly increased in SHR-sp rats. Antisense experiments revealed a functional importance of p28 for the beta-adrenergic growth response in isolated cardiomyocytes. Therefore, p28 seems causally involved in this beta-adrenergic growth response.
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PMID:Hypertrophy-associated gene induction after beta-adrenergic stimulation in adult cardiomyocytes. 1118 Oct 18

Oral tolerance is a long recognized method to induce peripheral immune tolerance. Oral tolerance has been used successfully to treat animal models of autoimmune diseases and is being tested in human diseases. Low doses of oral antigen induce active suppression, whereas high doses induce clonal anergy and deletion. Oral antigen preferentially generates a Th2(IL-4/IL-10)- or a Th3(TGF-beta)-type response. Th3-type cells are a unique T-cell subset which primarily secrete TGF-beta, provide help for IgA and have suppressive properties for Th1 and other immune cells. Th3-type cells appear distinct from the Th2 cells as CD4(+) TGF-beta-secreting cells with suppressive properties in the gut have been generated from IL-4-deficient animals. In vitro differentiation of Th3-type cells from Th0 precursors from TCR transgenic mice is enhanced by culture with TGF-beta, IL-4, IL-10 and anti-IL-12. Because regulatory T cells generated by oral antigen are triggered in an antigen-specific fashion but suppress in an antigen-nonspecific fashion, they mediate bystander suppression when they encounter the fed autoantigen at the target organ. Thus, mucosal tolerance can be used to treat inflammatory processes that are not autoimmune in nature. Mucosal antigen has also been used to treat animal models of stroke and of Alzheimer's disease. Induction of low-dose oral tolerance is enhanced by oral administration of IL-4 and IL-10. Coupling antigen to CTB or administration of Flt-3 ligand enhances oral tolerance. Anti-B7.2 but not anti-B7.1 blocks low-dose, but not high-dose oral tolerance. High-dose oral tolerance is blocked by anti-CTLA-4. CD25(+) CD4(+) regulatory T-cell function also appears to be related to TFG-beta.
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PMID:Oral tolerance: immune mechanisms and the generation of Th3-type TGF-beta-secreting regulatory cells. 1156 43

The zebrafish mutant violet beauregarde (vbg) can be identified at two days post-fertilization by an abnormal circulation pattern in which most blood cells flow through a limited number of dilated cranial vessels and fail to perfuse the trunk and tail. This phenotype cannot be explained by caudal vessel abnormalities or by a defect in cranial vessel patterning, but instead stems from an increase in endothelial cell number in specific cranial vessels. We show that vbg encodes activin receptor-like kinase 1 (Acvrl1; also known as Alk1), a TGFbeta type I receptor that is expressed predominantly in the endothelium of the vessels that become dilated in vbg mutants. Thus, vbg provides a model for the human autosomal dominant disorder, hereditary hemorrhagic telangiectasia type 2, in which disruption of ACVRL1 causes vessel malformations that may result in hemorrhage or stroke. Movies available on-line
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PMID:Disruption of acvrl1 increases endothelial cell number in zebrafish cranial vessels. 1205 Jan 47

Transforming growth factor (TGF)-beta activity is involved in several cardiovascular diseases owing to its effects on the growth of vascular smooth muscle cells and induction of extracellular matrix formation. We evaluated expression of TGF-beta in cardiovascular organs from stroke-prone spontaneously hypertensive rats (SHR-SP) which show severe cardiovascular damages with the development of hypertension. Twelve-week-old Wistar-Kyoto (WKY)/Izm rats and SHR-SP/Izm were loaded with 1% salt for 4 weeks. Aorta, heart and kidney were removed and evaluated histologically by hematoxylin-eosin staining. Expression of TGF-beta1 mRNA was evaluated by reverse transcription and polymerase chain reaction analysis in mRNA extracted with oligo dT-cellulose. Expression of TGF-beta1 protein was evaluated by Western blot analysis and immunohistochemical study in renal cortex. Whereas expression of TGF-beta1 mRNA was detected only in the heart of SHR-SP before salt loading, it was detected in the aorta, left ventricle of heart and renal cortex from both rat strains, and it was stronger in the renal cortex of SHR-SP than in the renal cortex of WKY rats. Expression of TGF-beta1 protein was markedly higher in the renal cortex of SHR-SP than in the renal cortex of WKY rats after salt loading. TGF-beta was localized at glomeruli and capillary arteries in the renal cortex, and immunostaining was stronger in SHR-SP than in WKY rats. Expression of TGF-beta1 was increased in glomeruli and capillaries of the renal cortex with the development of hypertension in SHR-SP. These results implicate TGF-beta in the renal damage observed in hypertension.
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PMID:Transforming growth factor-beta expression in cardiovascular organs in stroke-prone spontaneously hypertensive rats with the development of hypertension. 1248 16

The intravenous injection of the serine protease, tissue-type plasminogen activator (t-PA), has shown to benefit stroke patients by promoting early reperfusion. However, it has recently been suggested that t-PA activity, in the cerebral parenchyma, may also potentiate excitotoxic neuronal death. The present study has dealt with the role of the t-PA inhibitor, PAI-1, in the neuroprotective activity of the cytokine TGF-beta1 and focused on the transduction pathway involved in this effect. We demonstrated that PAI-1, produced by astrocytes, mediates the neuroprotective activity of TGF-beta 1 against N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity. This t-PA inhibitor, PAI-1, protected neurons against NMDA-induced neuronal death by modulating the NMDA-evoked calcium influx. Finally, we showed that the activation of the Smad3-dependent transduction pathway mediates the TGF-beta-induced up-regulation of PAI-1 and subsequent neuroprotection. Overall, this study underlines the critical role of the t-PA/PAI-1 axis in the regulation of glutamatergic neurotransmission.
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PMID:Smad3-dependent induction of plasminogen activator inhibitor-1 in astrocytes mediates neuroprotective activity of transforming growth factor-beta 1 against NMDA-induced necrosis. 1250 96

Several members of the FGF family, in particular FGF2, are intimately involved in neuronal protection and repair after ischemic, metabolic or traumatic brain injury. Expression of Fgf2 mRNA and protein is strongly upregulated after neuronal damage, with glial cells as the predominant source. Given its survival-promoting effects on cultured neurons, exogenous FGF2 was tested in several animal models of stroke and excitotoxic damage, in which it consistently proved protective against neuronal loss. FGF2 affords neuroprotection by interfering with a number of signaling pathways, including expression and gating of NMDA receptors, maintenance of Ca2+ homeostasis and regulation of ROS detoxifying enzymes. FGF2 prevents apoptosis by strengthening anti-apoptotic pathways and promotes neurogenesis in adult hippocampus after injury. The protective action of FGF2 has been linked to its augmenting effect on the lesion-induced upregulation of activin A, a member of the TGF-beta superfamily. Despite the well-documented benefits of FGF2 in animal models of stroke, there is currently no clinical development in stroke, after a phase II/III trial with FGF2 in acute stroke patients was discontinued because of an unfavorable risk-to-benefit ratio. As the molecular targets of FGF2 are going to be unraveled over the next years, new therapeutic strategies will hopefully emerge that enable us to influence the various protective mechanisms of FGF2 in a more specific fashion.
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PMID:Fibroblast growth factors and neuroprotection. 1257 27

Discordant findings are reported on the left ventricular transforming growth factor-beta(1) (TGF-beta(1)) mRNA levels in various rat models. Left ventricular TGF-beta(1) mRNA levels did not differ between spontaneously hypertensive rats (SHR) and normal rats, between deoxycorticosterone (DOCA)-salt and sham-operated hypertensive rats, but were increased in stroke-prone spontaneously hypertensive rats (SHRSP) and in post-myocardial infarction (MI) rats. Renal cortical TGF-beta(1) mRNA levels were, however, higher in DOCA-salt hypertensive rats. Angiotensin II subtype 1 receptor antagonism (AT(1)R) and angiotensin converting enzyme inhibition (ACEI) decreased left ventricular and vascular smooth muscle TGF-beta(1) mRNA levels in SHR and renal TGF-beta(1) mRNA in DOCA-salt hypertensive rats and in SHRSP. In post-MI rats ventricular TGF-beta(1) mRNA decreased by AT(1)R antagonism. In essential hypertensive patients, TGF-beta(1) protein as well as TGF-beta(1) mRNA levels are hyperexpressed. The TGF-beta(1) overproduction in hypertension can be attributed to various factors such as elevated angiotensin II, increased systemic blood pressure (BP) per se, increased fluid shear stress and a differential expression of TGF-beta(1) linked to DNA polymorphism in the promoter. The Arg(25) polymorphism in the TGF-beta(1) gene is associated with higher BP. A higher plasma TGF-beta(1) concentration is found in hypertensive patients with microalbuminuria and left ventricle hypertrophy. In these patients, AT(1)R antagonism and ACEI reduced these plasma TGF-beta(1) levels significantly.
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PMID:Association between transforming growth factor-beta and hypertension. 1285 Mar 97

Necrosis and apoptosis are the two fundamental hallmarks of neuronal death in stroke. Nevertheless, thrombolysis, by means of the recombinant serine protease t-PA, remains until now the only approved treatment of stroke in man. Over the last years, the cytokine termed Transforming Growth Factor-beta 1 (TGF-beta 1) has been found to be strongly up regulated in the central nervous system following ischemia-induced brain damage. Recent studies have shown a neuroprotective activity of TGF-beta 1 against ischemia-induced neuronal death. In vitro, TGF-beta 1 protects neurons against excitotoxicity by inhibiting the t-PA-potentiated NMDA-induced neuronal death through a mechanism involving the up-regulation of the type-1 plasminogen activator inhibitor (PAI-1) in astrocytes. Altogether, these observations suggest that either TGF-beta signaling or TGF-beta 1-modulated genes could be good targets for the development of new therapeutic strategies for stroke in man.
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PMID:[Does transforming growth factor-beta (TGF-beta) act as a neuroprotective agent in cerebral ischemia?]. 1291 Jun 29


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