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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemopoietic colony stimulating factors (HCSFs) are naturally occurred substances that are released in response to infection or inflammation and regulate the proliferation and differentiation of hemopoietic progenitor cells. Some representative members of this peptide family induce atherogenesis through the mediation of monocyte-endothelial cell adhesive interaction and promotion of angiogenesis within the atherosclerotic plaques. HCSFs, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), also promote post-infarction cardiac remodeling though the enhanced activation and infiltration of monocytes into injured myocardial tissue and through altered equilibrium of collagen deposition/degradation. On the other hand, exogenous administration of granulocyte colony-stimulating factor (G-CSF) or eythropoietin (EPO) in patients with chronic ischemic disease or recent myocardial infarction have lead to beneficial arteriogenesis or myocardial cell regeneration, thus preventing adverse cardiac remodeling. While GM-CSF may hold therapeutic potential as an inhibitor of lung fibrogenesis, G-CSF appears to promote fibrosis in the lungs. The pathophysiological role of HCSFs also depends on the timing of their action on cardiovascular remodeling, as well as on the target progenitor hematopoietic cell. This article summarizes current knowledge about the clinical and therapeutic implications of these factors in chronic artery disease, post-infarction cardiac remodeling, chronic heart failure and in pulmonary fibrosis.
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PMID:Hematopoietic colony stimulating factors in cardiovascular and pulmonary remodeling: promoters or inhibitors? 1684 67

First isolated in the early 1960s, doxorubicin (DOX) remains among the most effective anticancer drug ever developed. However, this drug has proven to be a double-edged sword because it also causes a cardiomyopathy that leads to a form of congestive heart failure that is usually refractory to common medications. It is hoped that a better understanding of the mechanisms underlying DOX's cardiotoxicity will enable development of therapies with which to prevent and/or treat the heart failure it causes. Suggested contributors to DOX-induced cardiomyopathy include formation of reactive oxygen species, apoptosis, inhibited expression of cardiomyocyte-specific genes, and altered molecular signaling. And taking these various contributors into consideration, a variety of approaches aimed at preventing or mitigating the cardiotoxicity of DOX have been tried, but so far, the ability of these treatments to protect the heart from damage has been limited. That said, one recent approach that shows promise is adjuvant therapy with a combination of hematopoietic cytokines, including erythropoietin, granulocyte colony-stimulating factor, and thrombopoietin. We suggest this approach to preventing DOX-induced cardiomyopathy is worthy of serious consideration for clinical use.
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PMID:Doxorubicin-induced cardiomyopathy from the cardiotoxic mechanisms to management. 1732 80

Our previous study reveals that connexin (Cx) 43 is targeted by ACh to prevent lethal arrhythmia. Granulocyte colony-stimulating factor (G-CSF), used against ischemic heart failure, may be another candidate, however, with unknown mechanisms. Therefore, we investigated the cellular effects of G-CSF. G-CSF activated the Wnt and Jak2 signals in cardiomyocytes, and up-regulated Cx43 protein and phosphorylation levels. In addition, G-CSF enhanced the localization of Cx43, beta-catenin and cadherin on the plasma membrane. G-CSF inhibited the reduction of Cx43 by enhancing Cx43 anchoring and sustained the cell-cell communication during hypoxia. Consequently, G-CSF suppressed ventricular arrhythmia induced by myocardial infarction. As a result, G-CSF could be used as a therapeutic tool for arrhythmia.
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PMID:Granulocyte colony-stimulating factor activates Wnt signal to sustain gap junction function through recruitment of beta-catenin and cadherin. 1788 12

Giant cell carcinoma (GCC) is a highly aggressive variant of sarcomatoid carcinoma of the lung. To date, however, there have been no reported cases of ovarian carcinoma mainly composed of GCC. Herein is reported the case of a 54-year-old Japanese woman with an undifferentiated ovarian carcinoma producing granulocyte colony-stimulating factor (G-CSF) and an inflammatory cytokine. Histologically, the tumor was composed of cohesive nests or discohesive pleomorphic mononucleated or multinucleated tumor giant cells, accompanied by inflammatory cell infiltration and emperipolesis. Immunohistochemically, the tumor cells were focally positive for epithelial membrane antigen and cytokeratin 7. Clinically, after the initial surgery, the tumor had rapid regrowth along with the production of G-CSF and an inflammatory cytokine. Adjuvant chemotherapy was administered but induced severe heart failure and severe neutropenia, probably due to the presence of hypercytokinemia and excess G-CSF. Upon the appearance of these fatal side-effects the chemotherapy was immediately discontinued and replaced with radiotherapy. The recognition of this type of ovarian tumor is important for clinical management, because adjuvant chemotherapy is the standard treatment for clinical management of epithelial ovarian cancer.
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PMID:Ovarian undifferentiated carcinoma resembling giant cell carcinoma of the lung. 1832 18

The cytokine granulocyte colony-stimulating factor (G-CSF) is produced by numerous cell types including immune and endothelial cells. G-CSF binding to its receptor G-CSF-R which belongs to the cytokine receptor type I family depends on the interaction of alpha-helical motifs of the former and two fibronectin type III as well as an immunoglobulin-like domain of the latter. It activates several signalling transduction pathways including PI3K/Akt, Jak/Stat and MAP kinase, thereby promoting survival, proliferation, differentiation and mobilisation of haematopoietic stem and progenitor cells. Accordingly, recombinant human (rh)G-CSF has been extensively used in clinical haematology and oncology to enable bone marrow transplantation or to treat chemotherapy-associated neutropenia. Using animal models it has been recently shown that G-CSF, alone or in combination with other cytokines such as stem cell factor (SCF), causes an accumulation of bone marrow-derived cells in the infarcted heart which, however, do not differentiate into cardiac cells. Nevertheless, since beneficial effects on structural and functional properties were observed in animal models of cardiac, brain and hindlimb ischaemia other mechanisms of G-CSF action must be operative. Recent evidence suggests paracrine effects mediated by the immigrated bone marrow-derived cells and/or direct effects of the cytokine on resident G-CSF-R expressing cells. In both cases these may include promotion of cellular survival, proliferation and differentiation. First clinical studies in patients with myocardial infarction, heart failure and stroke have been accomplished and are reviewed in this paper.
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PMID:Granulocyte colony-stimulating factor (G-CSF) for cardio- and cerebrovascular regenerative applications. 1839 54

We hypothesized that therapy, composed of antiapoptotic soluble Fas (sFas) gene transfer, combined with administration of the cardioprotective cytokine granulocyte colony-stimulating factor (G-CSF), would markedly mitigate cardiac remodeling and dysfunction following myocardial infarction (MI). On the 3rd day after MI induced by ligating the left coronary artery in mice, four different treatments were initiated: saline injection (Group C, n = 26); G-CSF administration (Group G, n = 27); adenoviral transfer of sFas gene (Group F, n = 26); and the latter two together (Group G+F, n = 26). Four weeks post-MI, Group G+F showed better survival than Group C (96 vs. 65%, P < 0.05) and the best cardiac function among the four groups. In Group G, the infarct scar was smaller and less fibrotic, whereas in Group F the scar was thicker, without a reduction in area, and contained abundant myofibroblasts and vascular cells; Group G+F showed both phenotypes. G-CSF exerted a beneficial effect on infarct tissue dynamics through antifibrotic and proliferative effects on granulation tissue; however, it also exerts an adverse proapoptotic effect that leads to thinning of the infarct scar. sFas appeared to offset the latter drawback. In vitro study using cultured myofibroblasts derived from the infarct tissue revealed that G-CSF increased proliferating activity of those cells accompanying activation of Akt and signal transducer and activator of transcription 3, while accelerating Fas-mediated apoptosis with increasing Bax-to-Bcl-2 ratio. The results suggest that combined use of G-CSF administration and sFas gene therapy is a potentially powerful tool against post-MI heart failure.
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PMID:Combined therapy with cardioprotective cytokine administration and antiapoptotic gene transfer in postinfarction heart failure. 1920 3

Cell based therapy has become a new and attractive option for the treatment of cardiac disease and heart failure. Although it has been demonstrated in vitro and in vivo that differentiation of non-differentiated cells (progenitor cells) into cardiomyocytes is able even in adult hearts the potential use of such transdifferentiation processes is limited by the small number of cells that home and engraft in the myocardium and complete the transdifferentiation process. Therefore, cell recruitment to the damaged heart is a major challenge to improve any cell based therapy. This process requires homing and engraftment of stem or progenitor cells. Major strategies to improve stem or progenitor cell homing are based on an improvement of stem or progenitor cell mobilization from the bone marrow. Strategies that have been shown to be successful are those that use granulocyte colony-stimulating factor (G-CSF). But although cell mobilization was indeed successful no major impact on hemodynamics was found. Alternatives are therefore needed and experimental studies use parathyroid hormone, statins, erythropoietin, and others in addition to or as an alternative to G-CSF. Although each of these procedures does have an impact on cell mobilization and homing none of these studies has provided a direct evidence that a major improvement on top of standard pharmacological therapy can be expected from such strategies. In conclusion, improvement of stem cell homing is a major challenge in the development of successful cell based therapies but not yet improved to a clinical relevant status. The underlying concepts of different strategies will be discussed here.
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PMID:Mechanisms that regulate homing function of progenitor cells in myocardial infarction. 1927 30

This study investigates the effects of granulocyte colony-stimulating factor (G-CSF) therapy in experimental chronic chagasic cardiomyopathy. Chagas disease is one of the leading causes of heart failure in Latin America and remains without an effective treatment other than cardiac transplantation. C57BL/6 mice were infected with 10(3) trypomastigotes of Trypanosoma cruzi, and chronic chagasic mice were treated with G-CSF or saline (control). Evaluations following treatment were functional, immunological, and histopathological. Comparing hearts of G-CSF-treated mice showed reduced inflammation and fibrosis compared to saline-treated chagasic mice. G-CSF treatment did not alter the parasite load but caused an increase in the number of apoptotic inflammatory cells in the heart. Cardiac conductance disturbances in all infected animals improved or remained stable due to the G-CSF treatment, whereas all of the saline-treated mice deteriorated. The distance run on a treadmill and the exercise time were significantly greater in G-CSF-treated mice when compared to chagasic controls, as well as oxygen consumption (VO(2)), carbon dioxide production (VCO(2)), and respiratory exchange ration (RER) during exercise. Administration of G-CSF in experimental cardiac ischemia had beneficial effects on cardiac structure, which were well correlated with improvements in cardiac function and whole animal performance.
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PMID:Granulocyte colony-stimulating factor treatment in chronic Chagas disease: preservation and improvement of cardiac structure and function. 1960 24

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic cytokine usually used in the treatment of patients with cancer. Studies have shown regenerative properties of bone marrow stem cell mobilization due to G-CSF in animals. Moreover, others effects related to G-CSF and independent of tissue regeneration were shown to be protective. As a result, this cytokine has been tested as a therapy for ischemic heart failure in humans. However, when this treatment was evaluated in clinical trials, the beneficial effects seen in small animals were not confirmed in infarcted patients. Thus, we sought to review the effects of G-CSF after an ischemic insult and on the progression of heart failure in animals and humans.
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PMID:Granulocyte colony-stimulating factor for ischemic heart failure: should we use it? 2068 Apr 42

Granulocyte colony-stimulating factor (G-CSF) is a known hematopoietic glycoprotein, and recent studies have revealed that G-CSF possesses other interesting properties. Oxidative stress is involved in many diseases, such as atherosclerosis, heart failure, myocardial infarction, Alzheimer disease, and diabetic retinopathy. This study was designed to examine whether G-CSF has a protective effect on endothelial cells against oxidative stress and to investigate whether G-CSF has a therapeutic role in ischemic vascular diseases. Expression of G-CSF (P < .01) and G-CSF receptor (P < .05) mRNA in human retinal endothelial cells (HRECs) was significantly up-regulated by oxidative stress. Treatment with 100 ng/mL G-CSF significantly reduced H(2)O(2)-induced apoptosis in HRECs from 61.7% to 41.4% (P < .05). Akt was phosphorylated in HRECs by G-CSF addition, and LY294002, a PI3K inhibitor, significantly attenuated the antiapoptotic effect of G-CSF (by 44.1%, P < .05). The rescue effect was also observed in human umbilical vein endothelial cells. In mouse oxygen-induced retinopathy model, G-CSF significantly reduced vascular obliteration (P < .01) and neovascular tuft formation (P < .01). G-CSF treatment also clearly rescued the functional and morphologic deterioration of the neural retina. A possibility of a novel therapeutic strategy for ischemic diseases through attenuating vascular regression using G-CSF was proposed.
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PMID:Granulocyte colony-stimulating factor attenuates oxidative stress-induced apoptosis in vascular endothelial cells and exhibits functional and morphologic protective effect in oxygen-induced retinopathy. 2105 98


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