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)

The Insulin-like growth factor-1 (IGF-1) system is dynamic and complex, involving many binding proteins, binding-protein-related proteases, and receptors. It has emerged in time as a powerful defence to life processes of many cytotypes, tissues and systems. Mainly in body metabolism, diabetes and cardiovascular system, but also in brain and kidney, IGF-1 plays a key role in maintaining homeostasis, increasing progenitor cell potential, and improving physiologic performance both in rest and stress conditions. Its vasculoprotective and insulin sensitizing ability exerts a protective role on flow-metabolism coupling and organs function. Therapeutical human use of recombinant human IGF-1 (rhIGF-1) has been widely applied only in Laron syndrome, while being verified in many randomized controlled trials to improve glycemic control in type 1 and type 2 diabetes, and proposed in neurological disease such as amyotrophic lateral sclerosis, multiple sclerosis and Alzheimer disease. Sparse evidence exists moreover about rhIGF-1 use in insulin resistance, burns, catabolic and post-surgery states, acute and chronic renal failure, amyotrophic lateral and multiple sclerosis, brain injury, and immunoincompetence. Along with these data, results are available on cardiovascular benefit of administration of other growth factors, such as erythropoietin and vascular endothelial growth factor, or on cardiovascular side effects of growth factor antagonists such as trastuzumab in cancer therapy. We intended therefore to summarize in this review available human and animals evidence about rhIGF-1 effects on different systems with insights on rhIGF-1 cardiovascular effects. In view of its ability to improve flow-metabolism coupling, IGF-1 could indeed represent a new cardiovascular disease treatment option for many cardiac disorders such as ischemic heart disease and heart failure.
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PMID:Recombinant human insulin-like growth factor-1: a new cardiovascular disease treatment option? 1885 38

The discovery of vascular endothelial growth factors (VEGFs) and their receptors has considerably improved the understanding of the development and function of endothelial cells. Each member of the VEGF family appears to have a specific function: VEGF-A induces angiogenesis (i.e. growth of new blood vessels from preexisting ones), placental growth factor mediates both angiogenesis and arteriogenesis (i.e. the formation of collateral arteries from preexisting arterioles), VEGF-C and VEGF-D act mainly as lymphangiogenic factors. The study of the biology of these endothelial growth factors has allowed a major progress in the comprehension of the genesis of the vascular system and its abnormalities observed in various pathologic conditions (atherosclerosis and coronary artery disease). The role of VEGF in the atherogenic process is still unclear, but actual evidence suggests both detrimental (development of a neoangiogenetic process within the atherosclerotic plaque) and beneficial (promotion of collateral vessel formation) effects. VEGF and other angiogenic growth factors (fibroblast growth factor), although initially promising in experimental studies and in initial phase I/II clinical trials in patients with ischemic heart disease or peripheral arterial occlusive disease, have subsequently failed to show significant therapeutic improvements in controlled clinical studies. Challenges still remain about the type or the combination of angiogenic factors to be administered, the form (protein vs. gene), the route, and the duration of administration.
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PMID:Vascular endothelial growth factors in cardiovascular medicine. 1900 27

Tanshinone IIA (Tan IIA), a derivative of phenanthrenequinone isolated from Salvia miltiorrhiza, has been widely used for treating cardiovascular diseases in China. In the present study, we assessed the effect of Tan IIA on cardiac function, vascular endothelial growth factor (VEGF) expression and angiogenesis on models of myocardial infarction (MI) in rats. The results demonstrated that TanIIA elicited a significantly cardioprotective effect by improving heart function, reducing infarct size, and increasing survival rate in MI rat. Our results offer, for the first time, further insight into Tan IIA promoting angiogenesis and up-regulating VEGF expression in MI rats due to the enhancement of hypoxia-inducible factor 1alpha mRNA expression, and provide a novel target for Tan IIA in the prevention and treatment of myocardial ischemia injury.
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PMID:Cardioprotective effects of tanshinone IIA on myocardial ischemia injury in rats. 1953 Apr 45

B-type natriuretic peptide (BNP) is a peptide hormone of myocardial origin with significant cardioprotective properties. Patients with myocardial ischemia present with high levels of BNP in plasma and elevated expression in the myocardium. However, the molecular mechanisms of BNP induction in the ischemic myocardium are not well understood. The aim of the investigation was to assess whether myocardial hypoxia induces the production of BNP in human ventricular myocytes. To test the hypothesis that reduced oxygen tension can directly stimulate BNP gene expression and release in the absence of hemodynamic or neurohormonal stimuli, we used an in vitro model system of cultured human ventricular myocytes (AC16 cells). Cells were cultured under normoxic (21% O(2)) or hypoxic (5% O(2)) conditions for up to 48 h. The accumulation of BNP, atrial natriuretic peptide (ANP), and vascular endothelial growth factor (VEGF) was then measured. Hypoxia stimulated the protein release of BNP and VEGF but not ANP. In concordance, the increased mRNA levels of BNP and VEGF but not ANP were found on culturing AC16 cells under hypoxic conditions. The analysis of the transcriptional activity of the hypoxia-inducible factor 1 (HIF-1) in nuclear extracts showed that HIF-1 activity was induced under hypoxic conditions. Finally, the treatment of AC16 cells with the HIF-1 inhibitor rotenone in hypoxia inhibited BNP and VEGF release. In conclusion, these data indicate that hypoxia induces the synthesis and secretion of BNP in human ventricular myocytes, likely through HIF-1-enhanced transcriptional activity.
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PMID:Hypoxia induces B-type natriuretic peptide release in cell lines derived from human cardiomyocytes. 1954 90

After acute myocardial infarction (AMI), reopening of a totally occluded infarct-related artery (IRA) at a subacute stage is still controversial in symptom-free patients. However, in patients with persistent ischemic symptoms and inadequate collaterals to the infarct area, recanalization is thought to provide beneficial effects. In addition to augmenting myocardial perfusion, we hypothesized that the benefit of recanalization involves the manipulation of circulating stem cell-mobilizing cytokines. This study included 30 patients with a totally occluded IRA and ongoing ischemic symptoms (the study group) and 30 patients with a partially occluded IRA (the control group). All patients underwent successful angioplasty and/or stenting. Before and immediately after the coronary intervention, blood granulocyte-colony-stimulating factor (G-CSF), stem-cell factor (SCF), vascular endothelial growth factor (VEGF), and stroma-derived factor-1 (SDF-1alpha) were measured. After recanalization, G-CSF levels significantly increased in the study group compared to the control group (P=0.03). SDF-1alpha levels in the study group decreased relative to the controls (P=0.02). However, no significant changes in VEGF or SCF levels between the two groups were found. In the multivariate analysis, reopening of a totally occluded IRA was independently and significantly associated with changes in G-CSF and SDF-1alpha levels after recanalization. In conclusion, our data suggest that the benefits of late reperfusion of a totally occluded IRA in patients with ongoing myocardial ischemia may involve mechanisms associated with stem cell-mobilizing and plaque-stabilizing cytokines. This study provides the rationale to investigate serial changes in cytokines and the numbers of circulating progenitors after reperfusion in the future.
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PMID:Late reperfusion of a totally occluded infarct-related artery increases granulocyte-colony stimulation factor and reduces stroma-derived factor-1alpha blood levels in patients with ongoing ischemia after acute myocardial infarction. 1960 48

Ischemic heart disease is the leading cause of death and the number of refractory severe patients is increasing. Therefore, it is crucial to develop new therapeutic strategies for severe ischemic heart disease. We found that a low-energy shock wave (SW) (about 10% of energy density that used for urolithiasis) effectively increases the expression of vascular endothelial growth factor (VEGF) in cultured endothelial cells. Based on this in vitro study, we have started in vivo studies and have demonstrated that extracorporeal cardiac shock wave therapy with a low-energy SW upregulates the expression of VEGF, induces neovascularization, and improves myocardial ischemia in a porcine model of chronic myocardial ischemia without any adverse effects in vivo. On the basis of the promising results in animal studies, we have subsequently developed a new, non-invasive angiogenic therapy with low-energy SW for ischemic heart disease. Our extracorporeal cardiac SW therapy improved symptoms and myocardial perfusion evaluated with stress-scintigraphy in patients with severe coronary artery disease without indication of percutaneous coronary intervention or coronary bypass surgery. Importantly, no procedural complications or adverse effects were noted. The SW therapy was also effective to ameliorate LV remodeling after acute myocardial infarction in pigs and to enhance angiogenesis in hindlimb ischemia in rabbits. Based on these animal studies, we are also conducting clinical studies in patients with acute myocardial infarction and those with peripheral artery disease. Thus, our extracorporeal cardiac SW therapy is an effective, safe, and non-invasive angiogenic strategy in cardiovascular medicine and its indication is now rapidly expanding.
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PMID:Extracorporeal shock wave therapy as a new and non-invasive angiogenic strategy. 1971 78

Angiogenesis, the process of forming new blood vessels, is a well established and clinically relevant feature of a variety of disease states. Whether blood vessels sprout in a given tissue environment depends on the balance between factors that stimulate angiogenesis and those that impede it. Potent pro-angiogenic factors such as vascular endothelial growth factor (VEGF) have been identified, validated, and successfully used in the clinic. Likewise, anti-angiogenic factors are also emerging as biologically relevant and therapeutically useful entities. PAR1 is a G protein-coupled receptor (GPCR) that participates in hemostasis and vascular development and that mediates the angiogenic activity of thrombin. PAR1 is activated through proteolytic cleavage of its first forty-one extracellular residues by a variety of proteases, most notably thrombin. However, little effort has focused on the forty-one-residue peptide fragment liberated during PAR1 activation. Tsopanoglou and colleagues have now demonstrated that this peptide, parstatin, has intriguing antiangiogenic activity, and, in a follow-up study, they demonstrate its potential pharmacological utility using a rat model of ischemic heart disease.
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PMID:Parstatin, a novel protease-activated receptor 1-derived inhibitor of angiogenesis. 1972 Jul 48

Aim of the study was to assess effect of myocardial revascularization on levels of factors of angiogenesis in early and remote period after intervention. Main group comprised 228 patients with ischemic heart disease (n=228, 194 men, 34 women, mean age 57+/-8.7 years). Coronary bypass surgery was carried out in 29 patients while other 199 were subjected to percutaneous coronary intervention (PCI). Analysis of data was performed in the group as a whole and in 2 subgroups distinguished in dependence on type of invasive treatment. Levels of factors of angiogenesis - vascular endothelial growth factor (VEGF), transforming growth factor beta (TGFbeta), and endostatin - were measured before, in 6 days, and 6 months after invasive treatment. Compared with healthy persons patients with IHD had significantly higher level of VEGF and significantly lower levels of TGFbeta and endostatin. On day 6 after revascularization in the group as a whole level of VEGF insignificantly rose while level of TGFbeta insignificantly decreased. In 6 months after invasive treatment significant lowering of VEGF level and significant increase of TGFbeta was noted. Endostatin level was measured at baseline and in 6 months after invasive treatment. Significant elevation of endostatin level took place after 6 months. Thus PCI and coronary bypass surgery lead to lowering of VEGF level and elevation of levels of TGFbeta in 6 days after intervention. In remote period reverse dynamics was observed: of VEGF level rose and those of TGFbeta and endostatin increased.
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PMID:[Effect of myocardial revascularization on dynamics of factors of angiogenesis in patients with ischemic heart disease]. 2003 74

Mesenchymal stem cell (MSC) infusion may reduce myocardial ischemic injury. TNF-alpha is a proinflammatory cytokine produced in large quantities during myocardial ischemia that can exert beneficial or detrimental effects on MSC function by binding to a 55-kd receptor (TNFR1) or a 75-kd receptor (TNFR2) on MSCs. We investigated whether genetic modification with ablation of TNFR1 and/or TNFR2 affects MSC-mediated protection against myocardial ischemic injury. The MSCs were harvested from wild-type mice (WT-MSCs) and knockout mice with ablation of TNFR1 and/or TNFR2 (TNFR1KO, TNFR2KO, and TNFR1/R2KO MSCs). After anesthesia was initiated via inhalation of isoflurane, myocardial ischemia was induced in rats via coronary artery ligation. Hearts were then injected with vehicle or MSCs (1 x 10 cells/mL). Myocardial function was assessed 28 days postsurgery with 2-dimensional echocardiograms and isolated heart perfusion. Myocardial tissue was collected for cytokine analysis and infarct measurements. We found that MSC treatment offered significant protection against myocardial ischemia, namely by decreasing infarct size, improving heart function, and decreasing ventricular remodeling compared with vehicle. Compared with WT-MSCs, TNFR1KO MSCs conferred increased cardiac protection, although TNFR2KO and TNFR1/R2KO MSCs conferred less cardiac protection. In addition, treatment with TNFR1KO MSCs was associated with decreased levels of proinflammatory cytokines and an increased level of vascular endothelial growth factor in the myocardium, whereas treatment with TNFR2KO or TNFR1/R2KO MSCs was associated with increased levels of proinflammatory cytokines and a decreased level of vascular endothelial growth factor compared with treatment with WT-MSCs. We conclude that MSC TNFR1 and TNFR2 play important roles in MSC-mediated cardiac protection after myocardial ischemia.
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PMID:Ablation of TNF-alpha receptors influences mesenchymal stem cell-mediated cardiac protection against ischemia. 2016 Jun 64

Transplantation of mesenchymal stem cells (MSC) improves repair and function recovery following myocardial infarction (MI), but underlying mechanisms remain to be elucidated. We hypothesize that MSC could achieve protection by paracrine effects through released mediators rather than direct cardiac regeneration. We sought to characterize the effects of MSC-secreted growth factors on extent of early recovery from MI. Swine subjected to acute MI by temporary balloon occlusion of the left anterior descending coronary artery using percutaneous techniques received intracoronary injection of either concentrated MSC-derived growth factors or control medium. Animals were killed at 7 days to evaluate early effects. Treatment with MSC-derived factors significantly reduced cardiac troponin-T elevation and improved echocardiographic parameters, including fractional area shortening, stroke volume, cardiac output, and wall motion score index. Quantitative evaluation of fibrosis by Verhoff staining revealed a reduction of the fibrotic area in the infarcted zone. Similarly, Masson's trichrome staining revealed reduced myocardial damage as demonstrated by areas of relatively preserved myocardium in the infarcted area. TUNEL assay demonstrated less cardiomyocyte apoptosis. Protein array detected the presence of angiogenic (vascular endothelial growth factor, endothelin, and epiregulin), anti-apoptotic (Galectin-3, Smad-5, sRFP-1, and sRFP-4) and anti-remodeling factors. Reverse transcription polymerase chain reaction confirmed the expression of these factors. In summary, a single intracoronary injection of concentrated biologically active factors secreted by MSC could achieve early protection of ischemic myocardium and improve cardiac repair and contractility. MSC-derived growth factors injection (rather than MSC themselves) should be evaluated as a novel therapy to treat ischemic heart disease, avoiding many practical and technical issues of cell therapy.
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PMID:Improved function and myocardial repair of infarcted heart by intracoronary injection of mesenchymal stem cell-derived growth factors. 2055 84


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