Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peptide growth factors have been reported to contribute to the atherogenic process, and they are known to mediate signals for vascular remodeling. Using syngeneic and allogeneic rat aorta transplant models, we analyzed the impact of cold ischemia time up to 24 hours and reperfusion injury on development of transplant arteriosclerosis during the first 2 months after transplantation. The expression of the transforming growth factor-beta (TGF-beta) family as well as the platelet-derived growth factor (PDGF) and its receptors was studied by use of immunohistochemistry, followed by semiquantitative evaluation and multivariate analysis. In the syngeneically transplanted aortas, the expression of TGF-beta 1, PDGF, and the two PDGF receptors in the neointima increased significantly with the extent of cold ischemia time. Furthermore, there was a significant induction of the latent TGF-beta binding protein in the neointima as well as TGF-beta 2 in the media, both correlating with the observation time after transplantation. In the allogeneic grafts, all examined proteins were already induced strongly 2 weeks after transplantation, even at the shortest ischemic period studied (1 hour). However, no positive correlation between growth factor expression and cold ischemia or observation time could be found. Double immunohistochemistry revealed that macrophages express PDGF and its receptors as well as TGF-beta 1. Smooth muscle cells express both types of PDGF receptors, and a few T cells express TGF-beta 1 as well as PDGF receptors. In summary, TGF-beta and PDGF are induced by allogeneic as well as ischemic stimuli in transplanted aortas, suggesting a role in the pathogenesis of transplant arteriosclerosis and representing a potential target for therapeutic intervention.
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PMID:Ischemia-induced transplant arteriosclerosis in the rat. Induction of peptide growth factor expression. 897 57

Platelet-derived growth factor BB (PDGF-BB) plays a central role in wound healing. Platelet-derived growth factor has been shown to accelerate healing in preclinical and clinical studies, but its wound-healing effects in older animals have not been examined. An ischemic incisional model in young female (5 months) and aged male (60 months) rabbits was used to determine the influence of platelet-derived growth factor on day 14 postwounding with reduced blood supply. Wounds in aged ischemic animals were severely impaired in breaking strength compared with their nonischemic control wounds and wounds in young animals (p < 0.001). Topical platelet-derived growth factor (10 microg per wound) partially reversed the reduction in breaking strength in aged ischemic animals but was ineffective in young animals. Histologic studies showed that new granulation tissue deposition and mononuclear cell infiltration was dramatically lower in ischemic wounds of aged animals compared with their control wounds as well as wounds from young animals under both nonischemic and ischemic conditions. Platelet-derived growth factor partially reversed this deficit in old ischemic wounds but not in young ischemic wounds. Epithelial growth was reduced in wounds from aged animals compared with wounds from young animals after 14 days of healing. Platelet-derived growth factor treatment increased ischemic wound epithelial growth in aged ischemic animals about threefold compared with paired controls. In conclusion, wound healing in aged rabbits was severely impaired by ischemia, and a single topical platelet-derived growth factor treatment partially reversed this deficit.
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PMID:Differential effects of platelet-derived growth factor BB in accelerating wound healing in aged versus young animals: the impact of tissue hypoxia. 904 2

Polymyositis (PM) and dermatomyositis (DM) are two major and distinct inflammatory myopathies. Cytokines, implicated in the immune process, have been recognized in the muscle tissue from PM and DM patients, but their functional in situ role has not been identified. We analyzed the expression of the signal transducer and activator of transcription 1 (STAT1), a molecule whose up-regulation indicates the interaction of cytokines, or growth factors, with their target receptors in muscle fibers and inflammatory infiltrates in PM and DM. An immunohistochemical analysis was performed using monoclonal antibodies to STAT1 in 57 muscle biopsies from 10 patients with DM, 10 with PM, and 37 controls. The profile of STAT1 up-regulation was also investigated in cultured muscle stimulated by interferon-gamma, epidermal growth factor, platelet-derived growth factor, and interleukin-2, using semiquantitative polymerase chain reaction and Western blot. High STAT1 expression was observed in many perifascicular atrophic muscle fibers from DM patients in 10/10 biopsies. In contrast, only a few muscle fibers undergoing necrosis were STAT1 positive in 2/10 patients with PM and in 2/37 controls. STAT1 reactivity was noted in most cells of the infiltrates in DM, PM, and controls. In vitro, STAT1 was stimulated by interferon-gamma but not by the other molecules studied. These results suggest that in DM, but not in PM, there is distinctive functional local cytokine activity able to increase STAT1 expression in muscle fibers. As interferon-gamma specifically activates STAT1 in vitro, this cytokine in conjunction with ischemia is probably involved in perifascicular muscle fiber pathology in DM.
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PMID:Signal transducer and activator of transcription 1 in human muscle: implications in inflammatory myopathies. 921 34

Our previous studies demonstrated coordinate expression of platelet-derived growth factor (PDGF) -B chain and beta-receptor in neurons at risk in the rat brain with focal ischemia. To clarify a role of the -B chain in the brain further, we examined whether PDGF-A or -B chain protects CA1 pyramidal neurons from delayed neuronal death after forebrain ischemia in rats. Pretreatment with PDGF-BB, but not -AA, at 120 ng/d for 2 days until forebrain ischemia was performed markedly ameliorated delayed neuronal death in CA1 pyramidal neurons on day 7 after ischemia. This neuroprotective effect of PDGF-BB was dose-dependent, and pretreatment with PDGF-BB at 240 ng/d showed almost complete inhibition of delayed neuronal death. In contrast, posttreatment with PDGF-BB at 120 ng/d starting 20 minutes after ischemia demonstrated no significant neuroprotective effect. The current study established marked neuroprotective actions of PDGF-BB in ischemic neuronal damage.
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PMID:Platelet-derived growth factor-BB, but not -AA, prevents delayed neuronal death after forebrain ischemia in rats. 934 35

Nerve growth factor, brain-derived neurotrophic factor, and other neurotrophic factors have been reported to have neuroprotective effects against global ischemia. To investigate whether the homodimer of platelet-derived growth factor B-chain (PDGF-BB) can protect neurons against focal temporary ischemia, PDGF-BB was administered to the rat brain for a prolonged period prior to, during, and after ischemia, since PDGF-BB protected rat neurons from global ischemia in our previous study. A total of 82 male Sprague-Dawley rats were used. Recombinant PDGF-BB, or saline was administered into the left neocortex via an implanted osmotic pump for 3 days (1.2 microg in total), 7 days (2 microgram or 4 microgram in total), or 14 days (4 microgram in total) pre-ischemia and 2 days post-ischemia. In an additional group, PDGF-BB (4 microgram in total) was administered for 14 days by osmotic pump and focal ischemia was induced after an additional 7-day interval following removal of the pump. Focal temporary ischemia was induced in the left MCA territory by bilateral CCA and MCA occlusion for 2 h. All rats were sacrificed 2 days after ischemia and the volume of cerebral infarct was analyzed using TTC staining. In a separate set of animals, regional cerebral blood flow (rCBF) was monitored by the hydrogen clearance method and laser Doppler flowmetry (LDF) of the neocortex after 14 days of intracerebral administration of PDGF-BB or saline. In the group receiving PDGF-BB (4 microgram in total) for 7 or 14 days pre-ischemia, there was a significant reduction of neocortical infarction compared to that in the control or saline-infused group. The size of cerebral infarct was smallest in the group that received PDGF-BB for 14 days, when ischemia was induced 7 days after removal of the pump. Regarding rCBF measurement, there were no significant differences in groups receiving PDGF-BB or saline infusion for 14 days. The potent neuroprotective effect of PDGF-BB on global ischemia was also demonstrated in the focal ischemia model. However, prolonged intracerebral infusion for 7 to 14 days was necessary to achieve a significant reduction of infarct volume. Neuroprotection was not due to increased collateral flow during ischemia.
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PMID:Induction of infarct tolerance by platelet-derived growth factor against reversible focal ischemia. 951 39

The present study was conducted to clarify the role of platelet-derived growth factor-B chain (PDGF-B) in neuronal death after ischemia. Transient forebrain ischemia was induced in Mongolian gerbils by occluding the bilateral carotid arteries for 5 min. We investigated PDGF-B expression in the hippocampus after ischemia by immunohistochemistry, Northern blotting and in situ hybridization histochemistry. The results showed that PDGF-B is expressed in control CAI and CA3 neurons. In CA1, the amount of the PDGF-B transcript immediately increased, then disappeared 2 days after ischemia. Delayed neuronal death followed 1 day later. However, PDGF-B immunoreactivity in CA1 rapidly decreased and disappeared 12 h after transient forebrain ischemia, proceeding to delayed neuronal death. In contrast, the expression of both PDGF-B protein and the transcript was well preserved throughout the study in CA3, which remained viable even after ischemia. Accordingly, the selective neuronal susceptibility in the CA1 to ischemia corresponded with rapid disappearance of PDGF-B. PDGF-B expression may contribute to neuroprotective effect after ischemia.
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PMID:Expression of platelet-derived growth factor after transient forebrain ischemia in the gerbil hippocampus. 960 May 93

Coronary angioplasty is used to treat coronary atherosclerotic disease in many patients. One problem with coronary angioplasty is the phenomenon of restenosis. Restenosis appears to be a universal response to arterial wall injury. The biological events that underlie restenosis are characterized by: platelet adhesion and aggregation at sites of damaged endothelium, and within dissections into the medial layers, release of platelet derived growth-promoting substances, inflammation of the injured medial zone, transformation, migration, and proliferation of smooth muscle cells of the media following their activation by growth-promoting substances, secretion of copious amounts of extracellular matrix material, and finally, termination of the growth process following regrowth of endothelium over the damaged area. More than a decade of research work has helped identify clinical correlates of restenosis after coronary angioplasty. Patient-related correlates include male gender, unstable angina, diabetes, and continued smoking after angioplasty. Lesion-related correlates include multilesion and multivessel procedures, higher post-angioplasty residual stenosis, proximal vessel location, location in the left anterior descending coronary artery, location in a vein graft, long lesions, and total occlusions. However, for the purposes of individual patient care, clinical correlates are not particularly helpful. No group of variables has predicted complete freedom from restenosis, and conversely no group of variables has reliably indicated its presence. All patients undergoing angioplasty will require some form of follow-up evaluation. Symptom status by itself has not been found to be useful for predicting restenosis. However, when symptom status is combined with exercise thallium-201 scintigraphy, performed 4-6 months after angioplasty, it is less than ideal, but has a negative predictive value of over 90%. This means that over 90% of patients who are asymptomatic and have no evidence of ischemia by thallium-201 scintigraphy, will not have angiographic restenosis. Numerous clinical trials have been performed in order to reduce or prevent restenosis. Almost all have been disappointing, while a few have been encouraging. Studies of antiplatelet agents such as aspirin, dipyridamole (Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA), and Ticlopidine (Syntex, Humgcao, Puerto Rico) have not shown efficacy, yet studies of an inhibitor of platelet-derived growth factor have been provocatively encouraging. No reduction in restenosis rates was found with the anticoagulants Coumadin (Du Pont Pharmaceuticals, Wilmington, DE, USA) and Heparin (Wyeth-Ayerst, Philadelphia, PA, USA). Fish oils (omega fatty acids) have been found in several clinical trials to provide modest, but encouraging, reductions in restenosis, but await further confirmation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Restenosis after coronary angioplasty. 1015 Oct 16

Various polypeptide growth factors are generally considered to be involved in the regulation of the nephrogenic process both after acute renal injury and during renal development. Because platelet-derived growth factor B-chain (PDGF-B) has been reported to be expressed in immature tubulus of the developing kidney, PDGF-B could play a role in the process of tubulogenesis. We examined the expression of PDGF-B and PDGF receptors alpha and beta and their localization in kidneys after ischemia/reperfusion injury. The mRNA expressions of PDGF-B, PDGFR-alpha, and PDGFR-beta were enhanced after injury. In the immunohistochemical analysis and/or in situ hybridization, PDGF-B and PDGFR-alpha, beta were expressed after reperfusion in the S3 segment of the proximal tubuli, where they were not expressed normally. The expressions of proliferating cell nuclear antigen and vimentin were concomitantly observed with PDGF-B and PDGFRs in the tubular cells of injured S3 segment at 48 hours after injury. Next, the inhibition of the PDGF-B/PDGFRs axis with either Trapidil or Ki6896, which was found to inhibit the phosphorylation of PDGFR-beta selectively, resulted in a rise of serum creatinine, higher mortality rate, abnormal regenerating process, and suppressed proliferation of tubular epithelial cells. These findings suggest that the PDGF-B/PDGFRs axis is involved in the proliferation of injured tubular cells and plays an important role in the regeneration of tubular cells from acute ischemic injury.
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PMID:Role of PDGF B-chain and PDGF receptors in rat tubular regeneration after acute injury. 1055 Mar 25

In a previous work we have shown that heparin, in the presence of ozone (O3), promotes a dose-dependent platelet aggregation, while after Ca2+ chelation with citrate, platelet aggregation is almost negligible. These results led us to think that aggregation may enhance the release of platelet components. We have here shown that indeed significantly higher amount of platelet-derived growth factor (PDGF), transforming growth factor beta1 (TGF-beta1) and interleukin-8 (IL-8) are released in a dose-dependent manner after ozonation of heparinised platelet-rich plasma samples. These findings may explain the enhanced healing of torpid ulcers in patients with chronic limb ischemia treated with O3 autohaemoteraphy (O3-AHT).
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PMID:Studies on the biological effects of ozone: 10. Release of factors from ozonated human platelets. 1070 74

Restenosis after percutaneous intervention remains a significant clinical problem. Although stent implantation has significantly reduced the rate of restenosis by approximately 25% to 33%, intimal hyperplasia within stents still limits long-term vessel patency. The clinical sequelea of this neointimal proliferation is more pronounced in certain patient subgroups, eg, patients with diatbetes mellitus, diffuse disease, smaller vessels, chronic total occlusions, and lesions located in saphenous vein bypass grafts. Pharmacologic agents studied to date have failed to prevent restenosis. Tranilast, a novel anti-inflammatory agent, interferes with the proliferation and migration of vascular smooth muscle cells (VSMCs) induced by platelet-derived growth factor and transforming growth factor beta-1. Basic and preliminary clinical studies conducted with tranilast in Japan have shown encouraging results in terms of reducing restenosis. The Prevention of Restenosis with Tranilast and its Outcomes study (PRESTO), a double-blind, placebo-controlled study (n = 11,500), will test the efficacy of two doses (300 and 450 mg twice a day) of tranilast administered for 1 and 3 months compared with placebo. The primary objective is to compare the composite clinical event rate (death, myocardial infarction, or the need for ischemia-driven target vessel revascularization) after 9 months in patients treated with tranilast or placebo. Angiographic and intravascular ultrasound studies will be peformed in order to assess the effects of tranilast on angiographic restenosis and the volume of intimal hyperplastic tissue. If successful, tranilast will be the first drug to reduce angiographic and clinical restenosis.
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PMID:Tranilast in the Therapy of Coronary Artery Disease. 1109 62


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