Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the presence of myocardial ischemia, chronic electrical stimulation of a latissimus dorsi (LD) cardiomyoplasty enhances extramyocardial collateral blood flow. We postulated that basic fibroblast growth factor (bFGF) may mediate extramyocardial collateral formation. To test this hypothesis, LDs from goats with cardiomyoplasties were probed for the presence of bFGF by Western blot analysis and immunohistochemistry. Three groups were studied: static LD cardiomyoplasty (group 1); LD cardiomyoplasty stimulated at a 2-Hz frequency for 6 weeks (group 2); and LD cardiomyoplasty electrically stimulated and given human recombinant bFGF (group 3). There was no evidence of bFGF in the left LDs of group 1 by Western blot. Basic fibroblast growth factor-like immunoreactive evidence was found in the left LDs of group 2 goats by both Western blot and immunohistochemistry. In the right LDs of group 2, bFGF-like material was found by immunohistochemistry but not by Western blot, which suggests that the tissue concentrations were low (near the limits of detection). The left LDs of group 3 were positive for bFGF by Western blot and immunohistochemistry. Group 3 right LDs were positive for bFGF by immunohistochemistry. Immunohistochemical findings in group 2 indicate that bFGF is present in goat skeletal muscle. Western blot data from groups 1 and 2 suggest that bFGF may be increased in chronically stimulated cardiomyoplasties. From findings in group 3, we conclude that exogenous bFGF does not downregulate, and may upregulate, endogenous production. These results support the possibility that skeletal muscle bFGF is an important factor in extramyocardial collateral formation.
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PMID:Basic fibroblast growth factor identified in chronically stimulated cardiomyoplasties. 752 9

Basic fibroblast growth factor (FGF) is a multifunctional peptide that may play an integral role in angiogenesis associated with coronary collateral formation and myocardial infarct healing. We sought to determine the effects of exogenously administered basic FGF on collateral blood flow to ischemic myocardium. Ameroid constrictors were used to cause gradual occlusion of the left circumflex coronary artery in dogs. Basic FGF (110 micrograms, n = 9) or saline (n = 12) was given as a daily bolus injection directly into the collateral-dependent zone, beginning 10 days after placement of the Ameroid and continuing for 28 days. Collateral flow was assessed weekly as the ratio of collateral to normal zone (CZ/NZ) blood flow during maximal pharmacologically induced coronary vasodilation. The CZ/NZ increased in both treated and control dogs as a function of time; however, transmural collateral flow in basic FGF-treated dogs significantly exceeded that of control dogs by the second week of treatment. Final CZ/NZ blood flow ratios were 0.49 +/- 0.05 and 0.35 +/- 0.02 in the treated and control groups, respectively (means +/- SE, P = 0.0002). Treatment with basic FGF was also associated with significant increases in the numerical density of distribution vessels and endothelial cell DNA synthesis within the CZ. We also found that basic FGF had acute effects as a coronary vasodilator. Thus exogenous administration of basic FGF enhances maximal collateral blood flow in dogs with myocardial ischemia secondary to single-vessel coronary occlusion, an effect that is likely mediated through the direct angiogenic effects of the peptide, although its acute vasodilatory effects may also play a role.
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PMID:Basic fibroblast growth factor enhances myocardial collateral flow in a canine model. 818 38

The effects of acidic fibroblast growth factor (FGF-1) and basic fibroblast growth factor (FGF-2) and a non mitogenic form of FGF1 on myocardial ischemia and reperfusion were assessed. Rats underwent 10 minutes of coronary artery occlusion followed by 24 hours of reperfusion. Creatinine kinase content of the affected myocardium showed that both fibroblast growth factors 1 and 2 effectively protected against ischemia reperfusion injury (p < 0.01), and that the vasoactive but nonmitogenic form of the FGF1 was equally protective (p < 0.01 versus control + vehicle). The results were confirmed by light and electron-microscopy histological studies. Histological evaluations after treatment with the non-mitogenic fibroblast growth factor 1 showed that it did not generate the severe hyperplasia and connective tissue disorganization observed with the native mitogenic proteins. The possibility of using a non-mitogenic form of fibroblast growth factor for cardio-protection circumvents many of the potentially undesirable effects that may derive from systemically introducing broad spectrum acting fibroblast growth factors in vivo. This myocardial protection observed 24 hours after the treatment with fibroblast growth factors, and the efficacy of the non-mitogenic form of the protein, also suggest that the protective effect of fibroblast growth factors may be due to the increased blood flow rather than to angiogenesis.
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PMID:Protection of rat myocardium by mitogenic and non-mitogenic fibroblast growth factor during post-ischemic reperfusion. 940 16

Intimal and/or medial hyperplasia of intramyocardial small vessels is thought to be one of the causes of myocardial ischemia in hypertrophic cardiomyopathy (HCM). However, the pathogenesis of such vascular lesions in HCM is not yet known. To evaluate the pathogenic role of platelet-derived growth factor (PDGF-B) and basic fibroblast growth factor (b-FGF), which have a potential to induce cellular and molecular changes observed in the vessels in HCM, we examined the expression of these molecules and PDGF receptors in cardiac tissues from six patients with HCM and seven controls using immunohistochemistry. The percentage of PDGF-B positive cells in the myocyte population in HCM was significantly higher than that in controls (52.6 +/- 16.2 (mean +/- SD) vs. 21.6 +/- 9.6, p < 0.01). PDGF-B was also observed in vascular regions in HCM (61.1 +/- 25.5% of arterioles) but not in controls. There were no significant differences in the expression of b-FGF and PDGF receptors in the myocyte and non-myocyte populations and the vascular regions between the HCM and control groups. Our study revealed that the expression of PDGF-B protein was up-regulated in HCM, suggesting the contribution of this molecule to the development of intramyocardial vasculopathy.
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PMID:Immunohistochemical analysis of platelet-derived growth factor-B expression in myocardial tissues in hypertrophic cardiomyopathy. 1072 27

Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) have both shown strong angiogenetic effects in ischemic animal models and it has been reported that these growth factors were increased after acute myocardial ischemia. However, there have been few reports on the serum levels of bFGF and VEGF after acute myocardial infarction (AMI), in particular there has not been a comparative study of bFGF and VEGF in human subjects. The time course of circulating levels of bFGF and VEGF was examined in 36 patients with AMI who were within 24h of the onset of the AMI. The serum bFGF and VEGF levels of 50 age- and sex-matched healthy volunteers served as the baseline value. All the patients had undergone coronary angiography on the day of admission (Day 0), but prior to that the serum bFGF and VEGF levels were examined by enzyme-linked immunoassay. The serum bFGF and VEGF levels were also evaluated on Days 7, 14 and 28. Creatine kinase, myosin light chain I and troponin-T were measured subsequently and radionuclide examinations were performed during the early phase of AMI to determine the infarct size. The serum bFGF levels were significantly increased at Day 0 and were maintained until Days 7 and 14. Although serum VEGF levels at Day 0 were similar to the baseline values, they showed a remarkable increase by Days 7 and 14. A high serum level of bFGF was detected in the acute phase of AMI, and a later increase in VEGF was determined in the sub-acute phase, which suggest that these 2 growth factors play an important role at different time points of the reconstructing process of infarcted myocardial tissue.
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PMID:Elevated circulating levels of basic fibroblast growth factor and vascular endothelial growth factor in patients with acute myocardial infarction. 1094 14

The ability of organisms to spontaneously develop collateral vessels represents an important response to vascular occlusive diseases that determines the severity of residual tissue ischemia. Neovascularization of ischemic cardiac or skeletal muscle may be sufficient to preserve tissue integrity and/or function, and may thus be considered to be therapeutic. Innovative gene technologies and advances in animal modeling have enabled research scientists to develop therapeutic angiogenesis strategies applied in animal models of limb or myocardial ischemia and in treatment of patients with peripheral vascular obstruction or coronary artery diseases. Several therapeutic strategies have been proposed and tested even at the clinical level. Recent studies have established the feasibility of using recombinant angiogenic growth factors (mainly VEGF and FGF) to enhance angiogenesis in patients with limb or myocardial ischemia. Angiogenesis therapies using cells as a support for growth factor delivery or using endothelial progenitor cells which may directly participate in the angiogenic process have also been developed. Finally, one potential alternative strategy may be the use of drugs with pro-angiogenic activity, available in an oral formulation and which are currently administered to patients for treatment of different pathologies. All strategies of angiogenesis therapy currently being tested have the potential to be effective in the treatment of ischemic disease. However, such strategies may cause harmful side effects which emphasize the need to be aware of the biological effects of each angiogenic agent proposed for clinical studies.
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PMID:Angiogenesis therapy in ischemic disease. 1199 34

Therapeutic vascular growth in the treatment of peripheral and myocardial ischemia has not yet fulfilled its expectations in clinical trials. Randomized, double-blinded placebo-controlled trials have predominantly shown the safety and feasibility but not the clear-cut clinically relevant efficacy of angiogenic gene or recombinant growth factor therapy. It is likely that growth factor levels achieved with single injections of recombinant protein or naked plasmid DNA are too low to induce any relevant angiogenic effects. Also, the route of administration of gene transfer vectors has not been optimal in many cases leading to low gene-transfer efficacy. Animal experiments using intramuscular or intramyocardial injections of adenovirus encoding vascular endothelial growth factor (VEGF, VEGF-A), the mature form of VEGF-D, and fibroblast growth factors (FGF-1, -2, and -4) have shown high angiogenic efficacy. Adenoviral overexpression of VEGF receptor-2 ligands, VEGF-A and the mature form of VEGF-D, enlarge the preexisting capillaries in skeletal muscle and myocardium via nitric oxide(NO)-mediated mechanisms and via proliferation of both endothelial cells and pericytes, resulting in markedly increased tissue perfusion. VEGF also enhances collateral growth, which is probably secondary to increased peripheral capillary blood flow and shear stress. As a side effect of VEGF overexpression and rapid microvessel enlargement, vascular permeability increases and may result in substantial tissue edema and pericardial effusion in the heart. Because of the transient adenoviral gene expression, the majority of angiogenic effects and side effects return to baseline by 2 weeks after the gene transfer. In contrast, VEGF overexpression lasting over 4 weeks has been shown to induce the growth of a persistent vascular network in preclinical models. To improve efficacy, the choice of the vascular growth factor, gene transfer vector, and route of administration should be optimized in future clinical trials. This review is focused on these issues.
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PMID:Gene transfer for therapeutic vascular growth in myocardial and peripheral ischemia. 1552 34

We have previously shown that intracoronary delivery of recombinant adenoviruses encoding angiogenic proteins that contain signal peptides (fibroblast growth factor-4 and fibroblast growth factor-5) ameliorate myocardial ischemia. In the present paper, we test the hypothesis that the presence of the signal peptide is an important element in the favorable effects that transgene expression has on regional flow and function in an animal model of myocardial ischemia. We performed intracoronary delivery of two different recombinant adenoviruses encoding a fibroblast growth factor-2 variant, one with a signal peptide, FGF-2LI(+sp), and one without a signal peptide, FGF-2LI(-sp). In a model of stress-induced myocardial ischemia, intracoronary injection of these recombinants resulted in mRNA and protein expression of the transferred gene. Two weeks after gene transfer, regional abnormalities in stress-induced function and blood flow were improved after delivery of FGF-2LI containing the signal peptide. In the absence of the signal peptide, perfusion was not improved, and function was improved to a lesser degree than with FGF-2LI containing the signal peptide. These studies indicate that the presence of a signal peptide increases the efficacy of treatment and may reduce the required recombinant adenovirus dose for a given effect, and thereby provide an important safety margin for clinical application.
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PMID:Signal peptide increases the efficacy of angiogenic gene transfer for treatment of myocardial ischemia. 1614 4

We have a new therapeutic modality, regenerative medicine, for patients with severe ischemic heart disease. Growth factor administration and cell transplantation are available. Therapeutic angiogenesis with bone marrow cell transplantation has been used clinically with favorable results. Basic fibroblast growth factor slow-release administration has recently started to be used clinically as another angiogenic therapy. It is more potent when combined with a donor artery and omentum (Bio-CABG). Myogenic cell transplantation is in clinical trials aimed at myocardial regeneration. However, it remains unresolved how transplanted myoblasts improve cardiac function and how we can prevent fatal arrhythmia. Many are researching cardiac stem cells and embryonic stem cells as candidates for myocardial regeneration. Recently, the paracrine effects of transplanted mesenchymal stem cells in the ischemic heart have been reported to contribute to improved cardiac function. Therefore, growth factors and cytokines may play an important role in the regeneration process induced by transplanted cells. We combined cell transplanstation with growth factor administration as well as reconstructive surgery for dilated left ventricle, which yielded excellent results. Our integrated strategy may result in the maximal benefits to patients in the future.
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PMID:[Therapeutic angiogenesis and myocardial regenerative medicine for ischemic heart disease]. 1648 94

Coronary heart disease remains one of the main problems in healthcare systems in western countries. Despite a vast improvement in revascularisation techniques in recent years, we still encounter many patients, who are not suitable for conventional revasularisation methods. A delivery of proangiogenic substances like VEGF or FGF to cardiac muscle was thought to help these patients. Nevertheless, in order to induce angiogenesis in heart in safe and efficient manner further studies of mechanism regulating vessel growth are necessary. This interest resulted in still increasing number of papers dealing with angiogenesis in heart. Still, the results of clinical studies were in large part discouraging. Therefore novel angiogenic substances are currently under investigation. The great expectations are associated with proteins affecting multiple levels and processes involved in vessel growth and maturation. These include among others PIGF and CYR61. Other promising approach is the induction of angiogenesis by stem cells and endothelial progenitor cells. Hopefully these efforts will soon reveal therapeutic methods, which will be applicable in patients with severe ischemic heart disease disqualified from conventional revascularisation procedures.
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PMID:[Angiogenesis in heart]. 1818 32


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