Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gene transfer for therapeutic angiogenesis represents a novel treatment for patients with chronic angina refractory to standard medical therapy and not amenable to conventional revascularization. We sought to assess the role of intraoperative multiplane transesophageal echocardiography (MPTEE) in guiding injection of naked DNA encoding vascular endothelial growth factor (VEGF) into the left ventricular (LV) myocardium of patients with refractory angina. After exposing the LV myocardium via a limited lateral thoracotomy, each of 17 patients in this series received 4 separate injections of VEGF DNA into different myocardial sites. Initial injections in the first patient produced intracavitary microbubbles, indicating injection of DNA into the LV chamber. Subsequently, each injection was preceded by a test injection of agitated saline. The absence of microbubbles while visualizing the LV cavity during the test injection verified that the ensuing injection of DNA would not be inadvertently squandered in the LV chamber itself. Intracavitary LV microbubbles were observed by MPTEE in 13 of 64 (20.3%) saline test injections and in 8 of 16 (50.0%) patients in which saline test injection was used, leading to adjustments in needle position. MPTEE imaging detected a previously unknown large, apical left ventricular thrombus in one patient, thereby preventing inadvertent injection of VEGF DNA through the myocardium into the thrombus. Imaging during and after injection verified no deleterious impact on LV function. We conclude that MPTEE is a useful tool for ensuring that myocardial gene therapy performed by direct needle injection results in gene transfer to the LV myocardium.
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PMID:Intraoperative multiplane transesophageal echocardiography for guiding direct myocardial gene transfer of vascular endothelial growth factor in patients with refractory angina pectoris. 1051 50

The time course of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) release in patients with acute myocardial infarction (AMI) is unknown. Blood samples were obtained at the time of admission and 3, 7, 14 and 21 days later in 32 patients with AMI and 30 control patients. Serum VEGF and HGF, as well as C-reactive protein (CRP) and amyloid A protein (SAA), were determined. Both serum VEGF and HGF levels on admission in patients with AMI were higher than control values and peaked on day 7. VEGF levels in patients with preinfarction angina were higher than in patients with no preinfarction angina, whereas the HGF level did not differ. Both CRP and SAA levels peaked on day 3, and the CRP level on day 3 correlate with both VEGF and HGF levels on day 7. We hypothesized that the serum VEGF level is associated with preinfarction ischemia and the increase in VEGF and HGF on day 7 of AMI may represent a response to acute inflammation.
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PMID:Serial changes in serum VEGF and HGF in patients with acute myocardial infarction. 1096 88

In animal models of ischemia, a large body of evidence indicates that administration of angiogenic growth factors, either as recombinant protein or by gene transfer, can augment nutrient perfusion through neovascularization. While many cytokines have angiogenic activity, the best studied both in animal models and clinical trials are vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). Clinical trials of therapeutic angiogenesis in patients with end-stage coronary artery disease have shown large increases in exercise time and marked reductions in symptoms of angina, as well as objective evidence of improved perfusion and left ventricular function. Larger scale placebo-controlled trials have been limited to intracoronary and intravenous administration of recombinant protein, and have not yet shown significant improvement in either exercise time or angina when compared to placebo. Larger scale placebo-controlled studies of gene transfer are in progress. Future clinical studies will be required to determine the optimal dose, formulation, route of administration and combinations of growth factors, as well as the requirement for endothelial progenitor cell or stem cell supplementation, to provide effective and safe therapeutic myocardial angiogenesis.
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PMID:Therapeutic angiogenesis for ischemic cardiovascular disease. 1118 Oct 8

Acidic fibroblast growth factor (FGF) is a potent mitogen that can induce angiogenesis in vivo. We have recently reported a marked increase of basic FGF in the pericardial fluid of patients with severe coronary stenosis and an increase in vascular endothelial growth factor (VEGF) in the pericardial fluid of patients with severe myocardial ischemia. The purpose of this study was to evaluate whether acidic FGF levels in the pericardial fluid are associated with severe myocardial ischemia. Immediately after incision of the pericardium in 48 patients during open-heart surgery, 3-5ml of pericardial fluid was obtained. Concentrations of basic FGF and VEGF in the pericardial fluid were measured using an enzyme-linked immunosorbent assay (ELISA). The ELISA system for human acidic FGF was newly developed using a rabbit antibovine acidic FGF antibody. The patients were divided into three groups (group A: 13 patients undergoing emergency coronary artery bypass grafting (CABG) for unstable angina; group B: 17 patients undergoing elective CABG for stable angina; group C: 18 patients undergoing nonischemic open-heart surgery). The VEGF level in the pericardial fluid in group A was 68 +/- 59pg/ml, which was significantly higher than 33 +/- 9 pg/ml in group B and 31 +/- 20 pg/ml in group C (P < 0.05). The concentrations of basic FGF in the pericardial fluid in groups A and B were 722 +/- 601 and 773 +/- 763pg/ml, respectively, significantly higher than 263 +/- 349pg/ml in group C. The pericardial acidic FGF level in group A was 4,291 +/- 2,336 pg/ml, which was also significantly higher than 2,386 +/- 1,048 pg/ml in group B and 2,589 +/- 990 pg/ml in group C (P < 0.05). The acidic FGF level correlated well with the level of VEGF (r = 0.61, P < 0.0001). It is concluded that the level of acidic FGF in pericardial fluid is associated with severe myocardial ischemia. This result indicates that the release of acidic FGF from the myocardial tissue into pericardial fluid is closely related to severe myocardial ischemia.
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PMID:Myocardial ischemia enhances the expression of acidic fibroblast growth factor in human pericardial fluid. 1128 98

Recent progress in molecular biology has led to the development of gene therapy as a new strategy to treat a variety of cardiovascular diseases. Targeted diseases range from single gene deficiency diseases to more complex diseases in adults such as restenosis after angioplasty. One obvious major target in the field of gene therapy is ischemic diseases such as myocardial infarction, angina and peripheral arterial diseases (i.e. ASO (arteriosclerosis obliterans)). In a large proportion of such patients, the anatomical extent and the distribution of arterial occlusive disease make the patients unsuitable for operative or percutaneous revascularization. Thus, the disease frequently follows an inexorable downhill course. Of importance, there is no optimal medical therapy for severe ischemic hearts and critical ischemic limbs. Therefore, novel therapies are required to treat these patients. Recently, the efficacy of therapeutic angiogenesis using VEGF (vascular endothelial growth factor) gene transfer has been reported in human patients with critical limb ischemia and myocardial ischemia. Thus, the strategy for therapeutic angiogenesis using angiogenic growth factors should be considered for the treatment of patients with critical limb ischemia or myocardial infarction. The endothelial cell specificity of VEGF has been considered to be an important advantage for therapeutic angiogenesis, as endothelial cells represent the critical cellular element responsible for new vessel formation. Indeed, human gene therapy for ASO and angina has already begun in the USA, with surprising and beneficial effects. We have focused on hepatocyte growth factor (HGF), which is a mesenchyme-derived pleiotropic factor that regulates cell growth, cell motility, and morphogenesis in various types of cells. Recently, HGF is also considered to be a powertul growth tactor for endothelial cells. In this review, we described the potential gene therapy for ischemic diseases using HGF.
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PMID:Therapeutic angiogenesis induced by hepatocyte growth factor: potential gene therapy for ischemic diseases. 1142 85

A large body of evidence in animal models of ischemia shows that administration of angiogenic growth factors, either as recombinant protein or by gene transfer, can augment nutrient perfusion through neovascularization. Many cytokines have angiogenic activity; those that have been best studied in animal models and clinical trials are vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). Clinical trials of therapeutic angiogenesis in patients with end-stage coronary artery disease have shown increases in exercise time and reductions in anginal symptoms and have provided objective evidence of improved perfusion and left ventricular function. Larger-scale placebo-controlled trials have been limited to intracoronary and intravenous administration of recombinant protein and have not yet shown significant improvement in exercise time or angina compared with placebo. Larger-scale placebo-controlled studies of gene transfer are in progress. Clinical studies are required to determine the optimal dose, formulation, route of administration, and combinations of growth factors and the utility of adjunctive endothelial progenitor-cell or stem-cell supplementation, to provide safe and effective therapeutic myocardial angiogenesis. Determination of which growth factors or cells are required to optimize therapeutic neovascularization in an individual patient should be a goal of future research.
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PMID:Therapeutic angiogenesis for coronary artery disease. 1177 64

Research in animal models of ischemia has shown that administration of angiogenic growth factors, either as a recombinant protein or by gene transfer, can augment nutrient perfusion through neovascularization to promote the development of supplemental collateral blood vessels that will constitute endogenous bypass conduits around occluded native arteries; a strategy termed "therapeutic angiogenesis." In animal models and clinical trials, the best studied cytokines with angiogenic activity are vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). Clinical trials of therapeutic angiogenesis in patients with critical limb ischemia demonstrated resolution of rest pain and/or improved limb integrity, increased pain-free walking time and ankle-brachial index, newly visible collateral vessels by digital subtraction angiography, and qualitative evidence of improved distal flow by magnetic resonance imaging. Initial clinical trials in patients with end-stage coronary artery disease using direct myocardial injection via thoracotomy resulted in large increases in exercise time and marked reductions in anginal symptoms, as well as objective evidence of improved perfusion and left ventricular function. Larger scale placebo-controlled trials have been limited to intracoronary and intravenous administration of recombinant protein, and have not shown significant improvement in exercise time or angina compared to placebo. Larger scale placebo-controlled studies of gene transfer using catheter-based endocardial delivery are in progress. Future clinical studies are required to determine the optimal dose, formulation, route of administration, and combinations of growth factors, as well as the requirement for endothelial progenitor cell or stem cell supplementation, to provide effective and safe therapeutic angiogenesis for patients with critical limb ischemia and chronic myocardial ischemia who are not candidates for conventional revascularization procedures.
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PMID:Therapeutic angiogenesis in critical limb and myocardial ischemia. 1205 43

A placebo-controlled, double-blind, randomized study found that subjects randomized to the vascular endothelial growth factor (VEGF) gene-receiving treatment group showed a greater level of angina reduction in comparison to control subjects who received saline as a placebo. These data provide hope for a new treatment option for those who are not candidates for invasive therapeutic procedures and are refractory to medical therapy for angina. Furthermore, the findings are important to the areas of therapeutic angiogenesis and gene therapy as a whole. This article discusses VEGF and its brief history as a form of gene therapy in the context of the VEGF gene therapy trial that the American Heart Association has recognized as one of the top 10 scientific advances of 2001.
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PMID:Gene therapy with vascular endothelial growth factor reduces angina. 1253 88

This phase I open label, dose-escalating study shows that gene transfer of vascular endothelial growth factor-2 naked deoxyribonucleic acid by direct myocardial injection by way of thoracotomy in patients with Canadian Cardiovascular Society class 3 or 4 angina is feasible and safe. The procedure is well tolerated, with few major adverse cardiac events at 1 year, and without complications directly related to gene expression. In this prospective, nonblinded study, the procedure is associated with clinical improvement; however, there was no angiographic evidence of angiogenesis and there is a great potential for a sham or placebo effect in the study patients. A randomized phase III trial is underway that will help determine the efficacy of vascular endothelial growth factor-2 gene transfer in "no-option" patients.
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PMID:One-year follow-up of direct myocardial gene transfer of vascular endothelial growth factor-2 using naked plasmid deoxyribonucleic acid by way of thoracotomy in no-option patients. 1291 74

Although we reported that basic fibroblast growth factor (bFGF) levels in pericardial fluid of patients with unstable angina are apparently increased, it was unclear whether vascular endothelial growth factor (VEGF) is also increased in patients with myocardial ischemia. Using an enzyme-linked immunosorbent assay, we measured the concentrations of VEGF and bFGF in pericardial fluid of 51 patients with open heart surgery. Patients were divided into group A (n=10) with class III unstable angina (Braunwald's classification), group B (n=24) with class I or II unstable angina or stable angina and group C (n=17) with non-ischemic heart disease. The VEGF level in pericardial fluid in group A was 83+/-7 pg/ml, being significantly (p<0.001) higher than the 27+/-3 pg/ml in group B and the 28+/-5 pg/ml in group C. The concentrations of bFGF in pericardial fluid in groups A and B were 1461+/-579 and 1224+/-161 pg/ml, respectively, significantly (p<0.05) higher than the 292+/-97 pg/ml in group C. The level of VEGF in pericardial fluid was increased only in patients with severe rest angina within 2 days before emergency coronary artery bypass graft surgery (CABG), while bFGF was increased in all patients undergoing CABG for coronary artery disease. Thus VEGF and bFGF may play important roles in mediating collateral growth in humans.
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PMID:Marked elevation of vascular endothelial growth factor and basic fibroblast growth factor in pericardial fluid of patients with angina pectoris. 1451 80


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