Migration of bone marrow‐derived cells and improved perfusion after treatment with erythropoietin in a murine model of myocardial infarction

Brunner, Stefan; Hüber, Bruno; Weinberger, Tobias; Vallaster, Marcus; Wollenweber, Tim; Gerbitz, Armin; Hacker, Marcus; Franz, Wolfgang-Michael

doi:10.1111/j.1582-4934.2011.01286.x

Cited by 9 publications

(4 citation statements)

References 29 publications

(46 reference statements)

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“…(iv) Functionally, G-CSF significantly improved survival and preserved LV function after TAC procedure. In the last years, several studies focused on the endogenous repair mechanisms after mobilization of BMCs by cytokines, like G-CSF [9,11,18], parathyroid hormone [10,13,19,20] or erythropoietin [21,22] in ischaemic diseases like MI. It could be clearly demonstrated that the interaction of SDF-1 with its ligand CXCR4 plays a major role in the migration of BMCs into ischaemic cardiac tissue, which was associated with attenuated remodelling and improved function [12,23].…”

Section: Discussionmentioning

confidence: 99%

Attenuation of cardiac hypertrophy by G‐CSF is associated with enhanced migration of bone marrow‐derived cells

Hüber

Beetz

Laskowski

et al. 2015

J Cellular Molecular Medi

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Granulocyte-colony stimulating factor (G-CSF) has been shown to promote mobilization of bone marrow-derived stem cells (BMCs) into the bloodstream associated with improved survival and cardiac function after myocardial infarction. Therefore, the aim of the present study was to investigate whether G-CSF is able to attenuate cardiac remodelling in a mouse model of pressure-induced LV hypertrophy focusing on mobilization and migration of BMCs. LV hypertrophy was induced by transverse aortic constriction (TAC) in C57BL/6J mice. Four weeks after TAC procedure. Mice were treated with G-CSF (100 lg/kg/day; Amgen Biologicals) for 2 weeks. The number of migrated BMCs in the heart was analysed by flow cytometry. mRNA expression and protein level of different growth factors in the myocardium were investigated by RT-PCR and ELISA. Functional analyses assessed by echocardiography and immunohistochemical analysis were performed 8 weeks after TAC procedure. G-CSF-treated animals revealed enhanced homing of VLA-4 + and c-kit + BMCs associated with increased mRNA expression and protein level of the corresponding homing factors Vascular cell adhesion protein 1 and Stem cell factor in the hypertrophic myocardium. Functionally, G-CSF significantly preserved LV function after TAC procedure, which was associated with a significantly reduced area of fibrosis compared to control animals. Furthermore, G-CSF-treated animals revealed a significant improvement of survival after TAC procedure. In summary, G-CSF treatment preserves cardiac function and is able to diminish cardiac fibrosis after induction of LV hypertrophy associated with increased homing of VLA-4 + and c-kit + BMCs and enhanced expression of their respective homing factors VCAM-1 and SCF.

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Section: Discussionmentioning

confidence: 99%

Attenuation of cardiac hypertrophy by G‐CSF is associated with enhanced migration of bone marrow‐derived cells

Hüber

Beetz

Laskowski

et al. 2015

J Cellular Molecular Medi

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“…EPO is a growth factor exerting effects at diverse targets in addition to its well-known classical action to stimulate erythrocyte production. We have earlier found EPO to exert cardio-protective effects due to intrinsic anti-apoptotic properties and also due to mobilisation of bone marrow-derived stem cells [ 13 , 14 , 29 , 30 ]. The first clinical trial of EPO in patients with chronic heart failure gave promising findings of increased exercise capacity and cardiac function [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…Quantitative results were compared with reference standard LV-function measurements obtained with 1.5 T clinical MRI. We then proceeded to test gated FDG-PET for longitudinal monitoring in mice with CVB3-induced DCM after erythropoietin (EPO) treatment, based upon previous reports of its cardioprotective properties in preclinical models of myocardial infarction [ 13 , 14 ] as well as in rats with autoimmune-induced myocarditis [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Left ventricular functional assessment in murine models of ischemic and dilated cardiomyopathy using [18 F]FDG-PET: comparison with cardiac MRI and monitoring erythropoietin therapy

et al. 2012

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BackgroundWe performed an initial evaluation of non-invasive ECG-gated [18 F]FDG-positron emission tomography (FDG-PET) for serial measurements of left ventricular volumes and function in murine models of dilated (DCM) and ischemic cardiomyopathy (ICM), and then tested the effect of erythropoietin (EPO) treatment on DCM mice in a preliminary FDG-PET therapy monitoring study.MethodsMice developed DCM 8 weeks after injection with Coxsackievirus B3 (CVB3), whereas ICM was induced by ligation of the left anterior descending artery. LV volumes (EDV and ESV) and the ejection fraction (LVEF) of DCM, ICM and healthy control mice were measured by FDG-PET and compared with reference standard results obtained with 1.5 T magnetic resonance imaging (MRI). In the subsequent monitoring study, LVEF of DCM mice was evaluated by FDG-PET at baseline, and after 4 weeks of treatment, with EPO or saline.ResultsLV volumes and the LVEF as measured by FDG-PET correlated significantly with the MRI results. These correlations were higher in healthy and DCM mice than in ICM mice, in which LVEF measurements were somewhat compromised by absence of FDG uptake in the area of infarction. LV volumes (EDV and ESV) were systematically underestimated by FDG-PET, with net bias such that LVEF measurements in both models of heart disease exceeded by 15% to 20% results obtained by MRI. In our subsequent monitoring study of DCM mice, we found a significant decrease of LVEF in the EPO group, but not in the saline-treated mice. Moreover, LVEF in the EPO and saline mice significantly correlated with histological scores of fibrosis.ConclusionsLVEF estimated by ECG-gated FDG-PET significantly correlated with the reference standard MRI, most notably in healthy mice and mice with DCM. FDG-PET served for longitudinal monitoring of effects of EPO treatment in DCM mice.

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“…Growth factors, such as erythropoietin (EPO), can form a vital component for both neuronal and vascular cells and rely upon mTOR pathway signaling. EPO controls neuronal, inflammatory cell, and endothelial cell survival (Brunner et al , 2012; Caprara and Grimm, 2012; Chalhoub et al , 2012; Chong et al , 2002, 2003a; Eipel et al , 2012; Maiese et al , 2008b; Maiese et al , 2008d; Okaji et al , 2012; Shang et al , 2012; Talving et al , 2012). EPO governs mTOR signaling for microglia survival during oxidative stress (Shang et al , 2011) and for osteoblastogenesis and osteoclastogenesis (Kim et al , 2012).…”

Section: Stem Cell Proliferation and Differentiation With Mtormentioning

confidence: 99%

Shedding new light on neurodegenerative diseases through the mammalian target of rapamycin

Chong¹,

Shang

Wang

et al. 2012

Progress in Neurobiology

105

118

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Neurodegenerative disorders affect a significant portion of the world's population leading to either disability or death for almost 30 million individuals worldwide. One novel therapeutic target that may offer promise for multiple disease entities that involve Alzheimer's disease, Parkinson's disease, epilepsy, trauma, stroke, and tumors of the nervous system is the mammalian target of rapamycin (mTOR). mTOR signaling is dependent upon the mTORC1 and mTORC2 complexes that are composed of mTOR and several regulatory proteins including the tuberous sclerosis complex (TSC1, hamartin/ TSC2, tuberin). Through a number of integrated cell signaling pathways that involve those of mTORC1 and mTORC2 as well as more novel signaling tied to cytokines, Wnt, and forkhead, mTOR can foster stem cellular proliferation, tissue repair and longevity, and synaptic growth by modulating mechanisms that foster both apoptosis and autophagy. Yet, mTOR through its proliferative capacity may sometimes be detrimental to central nervous system recovery and even promote tumorigenesis. Further knowledge of mTOR and the critical pathways governed by this serine/threonine protein kinase can bring new light for neurodegeneration and other related diseases that currently require new and robust treatments.

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Migration of bone marrow‐derived cells and improved perfusion after treatment with erythropoietin in a murine model of myocardial infarction

Cited by 9 publications

References 29 publications

Attenuation of cardiac hypertrophy by G‐CSF is associated with enhanced migration of bone marrow‐derived cells

Attenuation of cardiac hypertrophy by G‐CSF is associated with enhanced migration of bone marrow‐derived cells

Left ventricular functional assessment in murine models of ischemic and dilated cardiomyopathy using [18 F]FDG-PET: comparison with cardiac MRI and monitoring erythropoietin therapy

Shedding new light on neurodegenerative diseases through the mammalian target of rapamycin

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