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)

Human hepatocyte GF (hHGF) has strong neoangiogenesis activity. The present study was designed to investigate the possible involvement of hHGF in neovascularization in proliferative diabetic retinopathy (PDR) by measuring vitreous hHGF concentrations. The mean vitreous hHGF concentration was higher in subjects with PDR (5.70 +/- 0.68 ng/mL, n = 33) than in nondiabetic control subjects (1.50 +/- 0.20 ng/mL, n = 18, P < 0.01), nondiabetic subjects with proliferative vitreoretinopathy (3.31 +/- 0.57 ng//mL, n = 10, P < 0.05), or diabetic subjects without PDR (1.29 +/- 0.28 ng/mL, n = 8, P < 0.01). PDR subjects with neovascularization of iris, which suggests advanced retinal ischemia, showed a higher mean vitreous hHGF concentration than those without iridal neovascularization [7.33 +/- 1.16 ng/mL (n = 14) vs. 4.49 +/- 0.72 ng/mL (n = 19), P < 0.05]. The mean vitreous hHGF concentration was higher in PDR subjects with retinal neovascularization at the optic disc than in those with neovascularization elsewhere [7.3 +/- 1.1 ng/mL (n = 15) vs. 4.4 +/- 0.7 ng/mL (n = 18), P < 0.05]. Our results indicate that vitreous hHGF may play a role in retinal neovascularization in PDR.
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PMID:Increased vitreous concentrations of human hepatocyte growth factor in proliferative diabetic retinopathy. 1002 34

Aberrant blood vessel growth in the retina that underlies the pathology of proliferative diabetic retinopathy and retinopathy of prematurity is the result of the ischemia-driven disruption of the normally antiangiogenic environment of the retina. In this study, we show that a potent inhibitor of angiogenesis found naturally in the normal eye, pigment epithelium-derived growth factor (PEDF), inhibits such aberrant blood vessel growth in a murine model of ischemia-induced retinopathy. Inhibition was proportional to dose and systemic delivery of recombinant protein at daily doses as low as 2.2 mg/kg could prevent aberrant endothelial cells from crossing the inner limiting membrane. PEDF appeared to inhibit angiogenesis by causing apoptosis of activated endothelial cells, because it induced apoptosis in cultured endothelial cells and an 8-fold increase in apoptotic endothelial cells could be detected in situ when the ischemic retinas of PEDF-treated animals were compared with vehicle-treated controls. The ability of low doses of PEDF to curtail aberrant growth of ocular endothelial cells without overt harm to retinal morphology suggests that this natural protein may be beneficial in the treatment of a variety of retinal vasculopathies.
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PMID:Prevention of ischemia-induced retinopathy by the natural ocular antiangiogenic agent pigment epithelium-derived factor. 1122 1

Vascular insufficiency and retinal ischemia precede many proliferative retinopathies and stimulate secretion of various vasoactive growth factors, including vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF). It is unclear, however, how PlGF, which is elevated in proliferative diabetic retinopathy and is a VEGF homolog that binds only to VEGF receptor (VEGFR)-1, promotes pathological angiogenesis. When primary microvascular endothelial cells were grown on collagen gels, PlGF-containing ligands upregulated Bcl-2 expression and stimulated the formation of capillary-like tube networks that were retained for up to 14 days in culture. The inhibition of VEGFR-1 results in a dramatic decrease in the number of capillary connections, indicating that VEGFR-1 ligands promote branching angiogenesis. In contrast, VEGF-induced tube formations and Bcl-2 expression were significantly decreased at the end of this period. Flow cytometry analysis of annexin-V/propidium iodide-stained cells revealed that PlGF and PlGF/VEGF heterodimer inhibited apoptosis in serum-deprived endothelial cells. These two growth factors stimulated a survival signaling pathway phosphatidylinositol 3-kinase (PI3K), as identified by increased Akt phosphorylation and because blocking PI3K signalling by adenovirus-mediated overexpression of wild-type phosphatase and tensin homolog on chromosome 10 (PTEN) disrupted angiogenesis and decreased Bcl-2 expression by PlGF and PlGF/VEGF heterodimer, whereas a dominant-negative PTEN mutant enhanced endothelial sprout formation and Bcl-2 expression. Together, these findings indicate that PlGF-containing ligands contribute to pathological angiogenesis by prolonging cell survival signals and maintaining vascular networks.
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PMID:Activation of vascular endothelial growth factor receptor-1 sustains angiogenesis and Bcl-2 expression via the phosphatidylinositol 3-kinase pathway in endothelial cells. 1463 57

Diabetic retinopathy is the most frequent cause of legal blindness in the population of 30-to-70-year olds. Whether retinopathy appears or not depends mainly on the duration of the disease and the degree of metabolic control the patient maintains. High blood glucose values lead to important changes in cellular metabolism and the main effects of these alterations are endothelial dysfunction that sets in motion the morphological process of diabetic retinopathy. The biochemical lesions caused by prolonged hyperglycemia can be positively influenced, but usually not normalized, pharmacologically with some groups of drugs, which are now under development. This makes tight control of glycemia a key measure in preventing the onset or progression of diabetic retinopathy, together with an effective program of ophthalmologic detection and follow-up in patients with diabetes. Regarding the role of endothelial dysfunction, antiplatelet drugs have been shown to slow some aspects of the evolution of diabetic retinopathy in its initial stages, mainly a lower degree of microaneurysms. However, a new approach to controlling endothelial dysfunction shows promise, mainly through the vascular endothelial growth factor (VEGF) inhibitors. These agents may prove to be especially useful in the treatment of proliferative diabetic retinopathy. Other encouraging results have been obtained in studies of antioxidant drugs and inhibitors of the formation of advanced glycation end products. Once retinal lesions appear, preventive measures need to be redoubled, with special attention to controlling glycemia; however, it is also necessary to resort to laser photocoagulation. This intervention aims to eliminate areas of ischemia and to diminish the formation of retinal exudates. If this measure fails or if vitreous hemorrhage appears, the only remaining therapeutic measure is vitrectomy.
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PMID:Pharmacological approach to diabetic retinopathy. 1503 85

The role of somatostatin and growth hormone in eye diseases recently became a matter of interest because of its link with proliferative diabetic retinopathy. In diabetic patients the pathologic proliferation of blood vessels as a result of retinal ischemia is a major cause of blindness. The hypoxic portions of the retina release angiogenic factors, stimulating neovascularization. Somatostatin is a natural peptide hormone that affects the release of a number of other hormones, such as growth hormone, glucagon, insulin and gastrin. The somatostatin analog promises to be safe and effective treatment for severe diabetic retinopathy. This compound has been shown to block the local and systemic production of insulin-like growth factor 1 and growth hormone, which promote the angiogenesis and endothelial cell proliferation associated with proliferative retinopathy. Several studies have confirmed that using somatostatin analogs to block insulin-like growth factor 1 production is effective in reducing neovascularization and preventing disease progression to proliferative stage of diabetic retinopathy. Long-acting somatostatin analogs are currently being tested for the treatment of diabetic retinopathy. The development of somatostatin analogs with increased selectivity for receptor subtypes will provide improved outcomes in the management of patients with diabetic retinopathy.
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PMID:Diabetes mellitus and retinopathy. 1507 18

Electroretinographic examinations were made in 191 patients with non-proliferative and pre-proliferative diabetic retinopathy. On the basis of the ratio of b-wave in ??? and ???? at 12 Hz, the glial index (Cg) was estimated for evaluating the functional changes in Muller cells. As the retinal ischemia aggravated, C@f was increasing, which was indicative of an activated metabolism of Muller cells. C@g was shown to be a sensitive criterion of retinal ischemia ensuring the detection of initial stages of retinal ischemia prior to the detection of changes recognizable in ophthalmoscopy and fluorescence angiography. The established regularities of changing functions in Muller glia and in glia-neuron ratios denote the possibility of using the electroretinographic criteria in the diagnosis of lesions in the retina and of early signs of retinal dystrophy in diabetic retinopathy.
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PMID:[Functional diagnosis of retinal ischemia. Communication 1. Reaction of Muller cells at early stages of diabetic retinopathy]. 1567 61

Electrography was made for 58 patients (110 eyes) with proliferative diabetic retinopathy distinguished by neovascularization. Fluorescence angiography and electroretinography were dynamically made for 1-1.5 years in 18 patients with preproliferative diabetic retinopathy. The hyperfunction of Muller cells with an increasing glial index, which was detected earlier by us in progressing retinal ischemia, was also observed in retinal neovascularization. The regular monitoring of the dynamics of electroretinogram (ERG, made several times) makes it possible to evaluate in each separate case a degree of neovascularization risk. When the value of the glial index abruptly drops in a patient, who had earlier regular increases in the index value, there is a high probability of a fast development of retinal neovascularization. Regular ERG examinations are advisable for the evaluation of a neovascularization risk.
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PMID:[Functional diagnostics of retinal ischemia: Muller cells and neovascularization of the retina in diabetic retinopathy]. 1575 43

Development of proliferative diabetic retinopathy's pathogenesis is still unknown. Last years publications seems to show immuno-inflammatory base of structural and functional retinal vessels endothelial cells' changes. Chronic retinal ischemia leads to development of pathological vessels and formation of fibrovascular tissue at the vitreoretinal interface. One of the important cause of the damage is leukocytes activation and adhesion to vascular endothelium, that is mediated by the specific adhesion molecules. Increase of soluble cellular adhesion molecules (CAMs) in serum, vitreous, epiretinal membranes of patients with PVR seems to confirm its role in the pathogenesis of this process. This publication attempts to estimate the CAM's role in progression of PDR.
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PMID:[The role of cellular adhesion molecule in the development of proliferative diabetic retinopathy]. 1611 51

Cardiovascular complications are the leading cause of morbidity and mortality in patients with diabetes mellitus; up to 80% of deaths in patients with diabetes are closely associated with vascular disease. The ability of the organism to form a collateral network of blood vessels constitutes an important response to vascular occlusive disease and determines to a large part the clinical consequences and severity of tissue ischemia. The development of new vessels is significantly reduced in diabetic patients with coronary or peripheral artery disease. This probably contributes to the severe course of limb ischemia in diabetic patients, in which peripheral artery disease often results in foot ulceration and lower extremity amputation. Diabetic retinopathy remains one of the major causes of acquired blindness in developed nations. This is true despite the development of laser treatment, which can prevent blindness in the majority of those who develop macular edema or proliferative diabetic retinopathy. The hallmark of diabetic retinopathy is the lack of microvessels in the macula, leading to hypoxia, associated with peripheral retinal neovascularization that may ultimately cause severe vitreous cavity bleeding and/or retinal detachment. The factors that stimulate retinal blood vessel growth have not been fully defined, but there is accumulating evidence that the renin-angiotensin-bradykinin system may be involved in a number of retinal vascular disorders, including retinopathy of prematurity and proliferative diabetic retinopathy. Only a few studies have specifically evaluated the effect of diabetes on angiogenesis in ischemic vascular disease and in the retina. Moreover, the mechanisms by which diabetes could both limit the formation of new blood vessels in most organs and simultaneously induce proliferative diabetic retinopathy remain largely undefined. In the present review, we aimed to briefly describe the main molecular mechanisms involved in the ischemia-induced angiogenesis, and their alterations in diabetes. Possible therapeutic strategies to restore angiogenesis in diabetic patients are also listed.
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PMID:[Diabetes and peripheral arterial occlusive disease: therapeutic potential and pro-angiogenic strategies]. 1670 93

Nitric oxide (NO) is an important mediator in ischemia-reperfusion injury during human orthotopic liver transplantation (OLT). The perioperative kinetics of nitrite/nitrate plasma levels in 25 patients undergoing uncomplicated OLT were studied. A uniform pattern with significant increases of nitrite/nitrate levels immediately after reperfusion was seen in all patients, followed by a decrease to pretransplant levels within 24h. Peak levels 30 min after reperfusion were correlated to the indocyanine green plasma disappearance rate (PDR(ICG)), suggesting an association of early released NO with graft perfusion in OLT.
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PMID:Perioperative kinetics of the nitric oxide derivatives nitrite/nitrate during orthotopic liver transplantation. 1690 45


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