GLORIA

GEOMAR Library Ocean Research Information Access

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • American Heart Association (AHA)  (11)
  • American Society of Hematology (ASH)  (4)
Document type
Keywords
Publisher
Years
  • 1
    facet.materialart.
    Unknown
    The function of hematopoietic stem cells is altered by both genetic and inflammatory factors in lupus mice (2013)
    American Society of Hematology (ASH)
    In: Blood
    Details
    Publication Date: 2013-03-15
    Description: Hematopoietic stem cells (HSCs) are protected in a metabolically dormant state within the bone marrow stem cell niche. Inflammation has been shown to disrupt HSC dormancy and cause multiple functional changes. Here, we investigated whether HSC functions were altered in systemic lupus erythematosus (SLE)-prone mice and whether this contributed to clinical manifestations of SLE. We found that HSCs were significantly expanded in lupus mice. The increase in HSC cellularity was caused by both genetic lupus risk factors and inflammatory cytokines in lupus mice. In addition, the inflammatory conditions of lupus led to HSC mobilization and lineage-biased hematopoiesis. Strikingly, these functionally altered HSCs possessed robust self-renewal capacity and exhibited repopulating advantages over wild-type HSCs. A single-nucleotide polymorphism in the cdkn2c gene encoding p18 INK4c within a SLE susceptibility locus was found to account for reduced p18 INK4c expression and the increase in HSC self-renewal capacity in lupus mice. Lupus HSCs with enhanced self-renewal capacity and resistance to stress may compete out transplanted healthy HSCs, thereby leading to relapses after HSC transplantation.
    Keywords: Hematopoiesis and Stem Cells
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology (ASH)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 2
    facet.materialart.
    Unknown
    Increased Oxidative Stress in the Nucleus Caused by Nox4 Mediates Oxidation of HDAC4 and Cardiac Hypertrophy [Integrative Physiology] (2013)
    American Heart Association (AHA)
    Details
    Publication Date: 2013-02-15
    Description: Rationale: Oxidation of cysteine residues in class II histone deacetylases (HDACs), including HDAC4, causes nuclear exit, thereby inducing cardiac hypertrophy. The cellular source of reactive oxygen species responsible for oxidation of HDAC4 remains unknown. Objective: We investigated whether nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4), a major nicotinamide adenine dinucleotide phosphate oxidase, mediates cysteine oxidation of HDAC4. Methods and Results: Phenylephrine (100 μmol/L), an α1 adrenergic agonist, induced upregulation of Nox4 (1.5-fold; P 〈0.05) within 5 minutes, accompanied by increases in O 2 – (3.5-fold; P 〈0.01) from the nuclear membrane and nuclear exit of HDAC4 in cardiomyocytes. Knockdown of Nox4, but not Nox2, attenuated O 2 – production in the nucleus and prevented phenylephrine-induced oxidation and nuclear exit of HDAC4. After continuous infusion of phenylephrine (20 mg/kg per day) for 14 days, wild-type and cardiac-specific Nox4 knockout mice exhibited similar aortic pressures. Left ventricular weight/tibial length (5.7±0.2 versus 6.4±0.2 mg/mm; P 〈0.05) and cardiomyocytes cross-sectional area (223±13 versus 258±12 μm 2 ; P 〈0.05) were significantly smaller in cardiac-specific Nox4 knockout than in wild-type mice. Nuclear O 2 – production in the heart was significantly lower in cardiac-specific Nox4 knockout than in wild-type mice (4116±314 versus 7057±1710 relative light unit; P 〈0.05), and cysteine oxidation of HDAC4 was decreased. HDAC4 oxidation and cardiac hypertrophy were also attenuated in cardiac-specific Nox4 knockout mice 2 weeks after transverse aortic constriction. Conclusions: Nox4 plays an essential role in mediating cysteine oxidation and nuclear exit of HDAC4, thereby mediating cardiac hypertrophy in response to phenylephrine and pressure overload.
    Print ISSN: 0009-7330
    Electronic ISSN: 1524-4571
    Topics: Medicine
    Published by American Heart Association (AHA)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 3
    facet.materialart.
    Unknown
    Monitoring Neuroprotective Effects Using Positron Emission Tomography With [11C]ITMM, a Radiotracer for Metabotropic Glutamate 1 Receptor [Basic Sciences] (2013)
    American Heart Association (AHA)
    In: Stroke
    Details
    Publication Date: 2013-08-28
    Description: Background and Purpose— Recent pharmacological evidence shows that antagonists for the metabotropic glutamate 1 (mGlu1) receptor exhibit neuroprotective effects in an ischemic brain. The aim of this study was to visualize the mGlu1 receptor and to monitor neuroprotective effects in a rat model of mild focal ischemia using positron emission tomography (PET) with N -[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-[ 11 C]methoxy- N- methylbenzamide ([ 11 C]ITMM), a radiotracer for mGlu1. Methods— Rats were subjected to a 30-minute transient right middle cerebral artery occlusion. Saline or minocycline, a neuroprotective agent, was intravenously injected immediately after surgery and then daily during the subsequent 7 days. PET imaging with [ 11 C]ITMM was performed on the rats on days 1 to 7 after ischemia. In vitro autoradiography and histopathologic staining were conducted to confirm the results of in vivo PET. Results— PET with [ 11 C]ITMM demonstrated a gradual decrease of radioactivity in the ipsilateral sides of the ischemic brains. The radioactivity uptake ratio between the ipsilateral and contralateral sides also decreased with time. Minocycline treatment slowed down the decrease in the radioactivity level in the ipsilateral sides. Pretreatment with JNJ16259685, an mGlu1-selective ligand, significantly reduced brain radioactivity, confirming that the uptake of [ 11 C]ITMM primarily reflects mGlu1 levels in the brain regions, including the ischemic area. In vitro autoradiography and histopathology confirmed the changes in mGlu1 levels in the brains. Conclusions— [ 11 C]ITMM-PET may be a useful technique for characterizing the change in mGlu1 level during the occurrence and progression of neuronal damage and for evaluating the neuroprotective effects of drugs after ischemia.
    Keywords: PET and SPECT
    Print ISSN: 0039-2499
    Electronic ISSN: 1524-4628
    Topics: Medicine
    Published by American Heart Association (AHA)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 4
    facet.materialart.
    Unknown
    FOXO1 repression contributes to block of plasma cell differentiation in classical Hodgkin lymphoma (2014)
    American Society of Hematology (ASH)
    In: Blood
    Details
    Publication Date: 2014-11-14
    Description: The survival of classical Hodgkin lymphoma (cHL) cells depends on activation of NF-B, JAK/STAT, and IRF4. Whereas these factors typically induce the master regulator of plasma cell (PC) differentiation PRDM1/BLIMP-1, levels of PRDM1 remain low in cHL. FOXO1, playing a critical role in normal B-cell development, acts as a tumor suppressor in cHL, but has never been associated with induction of PC differentiation. Here we show that FOXO1 directly upregulates the full-length isoform PRDM1α in cHL cell lines. We also observed a positive correlation between FOXO1 and PRDM1 expression levels in primary Hodgkin-Reed-Sternberg cells. Further, we show that PRDM1α acts as a tumor suppressor in cHL at least partially by blocking MYC. Here we provide a link between FOXO1 repression and PRDM1α downregulation in cHL and identify PRDM1α as a tumor suppressor in cHL. The data support a potential role for FOXO transcription factors in normal PC differentiation.
    Keywords: Lymphoid Neoplasia
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology (ASH)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 5
    facet.materialart.
    Unknown
    Varying Correlation Between 18F-Fluorodeoxyglucose Positron Emission Tomography and Dynamic Contrast-Enhanced MRI in Carotid Atherosclerosis: Implications for Plaque Inflammation [Brief Reports] (2014)
    American Heart Association (AHA)
    In: Stroke
    Details
    Publication Date: 2014-05-28
    Description: Background and Purpose— 18 F-fluorodeoxyglucose positron emission tomography and dynamic contrast-enhanced MRI have been proposed to quantitatively assess plaque inflammation by probing macrophages and neovessels, respectively. We examined their correlation to study the in vivo relationship between macrophage and neovessel activities in atherogenesis. Methods— Forty-one patients (34 men; aged 65±12 years) with a total of 68 carotid plaques (thickness ≥2 mm on ultrasound; 20 symptomatic) were assessed by both 18 F-fluorodeoxyglucose positron emission tomography/computed tomography and dynamic contrast-enhanced MRI within 2 weeks, measured as target-to-background ratio and transfer constant ( K trans ), respectively. Results— Overall, the correlation between target-to-background ratio and K trans was weak and marginal ( r =0.22; P =0.068). They were correlated in the symptomatic plaques ( r =0.59; P =0.006) but not in the asymptomatic plaques ( r =0.07; P =0.625; P =0.033 for difference in r ). Neither target-to-background ratio nor K trans was significantly higher in the symptomatic plaques, but both showed an inverse relationship with time since last neurological event ( r =–0.94 and –0.69 for target-to-background ratio and K trans , respectively). Conclusions— The correlation between 18 F-fluorodeoxyglucose positron emission tomography and dynamic contrast-enhanced MRI measurements varied with clinical conditions, pointing to a complex interplay between macrophages and neovessels under different pathophysiological conditions. The moderate correlation shown only in symptomatic plaques indicates the presence of acute plaque inflammation with increased metabolic activity and cytokine production by inflammatory cells.
    Keywords: Pathophysiology, Imaging, Carotid Stenosis, Mechanism of atherosclerosis/growth factors
    Print ISSN: 0039-2499
    Electronic ISSN: 1524-4628
    Topics: Medicine
    Published by American Heart Association (AHA)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 6
    facet.materialart.
    Unknown
    Deletion of Methionine Sulfoxide Reductase A Does Not Affect Atherothrombosis but Promotes Neointimal Hyperplasia and Extracellular Signal-Regulated Kinase 1/2 Signaling [Basic Sciences] (2015)
    American Heart Association (AHA)
    Details
    Publication Date: 2015-11-26
    Description: Objective— Emerging evidence suggests that methionine oxidation can directly affect protein function and may be linked to cardiovascular disease. The objective of this study was to define the role of the methionine sulfoxide reductase A (MsrA) in models of vascular disease and identify its signaling pathways. Approach and Results— MsrA was readily identified in all layers of the vascular wall in human and murine arteries. Deletion of the MsrA gene did not affect atherosclerotic lesion area in apolipoprotein E–deficient mice and had no significant effect on susceptibility to experimental thrombosis after photochemical injury. In contrast, the neointimal area after vascular injury caused by complete ligation of the common carotid artery was significantly greater in MsrA-deficient than in control mice. In aortic vascular smooth muscle cells lacking MsrA, cell proliferation was significantly increased because of accelerated G 1 /S transition. In parallel, cyclin D1 protein and cdk4/cyclin D1 complex formation and activity were increased in MsrA-deficient vascular smooth muscle cell, leading to enhanced retinoblastoma protein phosphorylation and transcription of E2F. Finally, MsrA-deficient vascular smooth muscle cell exhibited greater activation of extracellular signal-regulated kinase 1/2 that was caused by increased activity of the Ras/Raf/mitogen-activated protein kinase signaling pathway. Conclusions— Our findings implicate MsrA as a negative regulator of vascular smooth muscle cell proliferation and neointimal hyperplasia after vascular injury through control of the Ras/Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase 1/2 signaling pathway.
    Keywords: Animal Models of Human Disease, Smooth Muscle Proliferation and Differentiation, Genetically Altered and Transgenic Models, Restenosis, Vascular Disease
    Print ISSN: 1079-5642
    Electronic ISSN: 1524-4636
    Topics: Medicine
    Published by American Heart Association (AHA)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 7
    facet.materialart.
    Unknown
    NADPH Oxidase-Generated Reactive Oxygen Species Are Required for Stromal Cell-Derived Factor-1{alpha}-Stimulated Angiogenesis [Basic Sciences] (2014)
    American Heart Association (AHA)
    Details
    Publication Date: 2014-08-21
    Description: Objective— Reactive oxygen species (ROS) act as signaling molecules during angiogenesis; however, the mechanisms used for such signaling events remain unclear. Stromal cell–derived factor-1α (SDF-1α) is one of the most potent angiogenic chemokines. Here, we examined the role of ROS in the regulation of SDF-1α–dependent angiogenesis. Approach and Results— Bovine aortic endothelial cells were treated with SDF-1α, and intracellular ROS generation was monitored. SDF-1α treatment induced bovine aortic endothelial cell migration and ROS generation, with the majority of ROS generated by bovine aortic endothelial cells at the leading edge of the migratory cells. Antioxidants and nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitors blocked SDF-1α–induced endothelial migration. Furthermore, knockdown of either NOX5 or p22phox (a requisite subunit for NOX1/2/4 activation) significantly impaired endothelial motility and tube formation, suggesting that multiple NOXs regulate SDF-1α–dependent angiogenesis. Our previous study demonstrated that c-Jun N-terminal kinase 3 activity is essential for SDF-1α–dependent angiogenesis. Here, we identified that NOX5 is the dominant NOX required for SDF-1α–induced c-Jun N-terminal kinase 3 activation and that NOX5 and MAP kinase phosphatase 7 (MKP7; the c-Jun N-terminal kinase 3 phosphatase) associate with one another but decrease this interaction on SDF-1α treatment. Furthermore, MKP7 activity was inhibited by SDF-1α, and this inhibition was relieved by NOX5 knockdown, indicating that NOX5 promotes c-Jun N-terminal kinase 3 activation by blocking MKP7 activity. Conclusions— We conclude that NOX is required for SDF-1α signaling and that intracellular redox balance is critical for SDF-1α–induced endothelial migration and angiogenesis.
    Keywords: Angiogenesis, Cell signalling/signal transduction, Endothelium/vascular type/nitric oxide
    Print ISSN: 1079-5642
    Electronic ISSN: 1524-4636
    Topics: Medicine
    Published by American Heart Association (AHA)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 8
    facet.materialart.
    Unknown
    LRP1-Dependent Endocytic Mechanism Governs the Signaling Output of the Bmp System in Endothelial Cells and in Angiogenesis [Cellular Biology] (2012)
    American Heart Association (AHA)
    Details
    Publication Date: 2012-08-17
    Description: Rationale: Among the extracellular modulators of Bmp (bone morphogenetic protein) signaling, Bmper (Bmp endothelial cell precursor-derived regulator) both enhances and inhibits Bmp signaling. Recently we found that Bmper modulates Bmp4 activity via a concentration-dependent, endocytic trap-and–sink mechanism. Objective: To investigate the molecular mechanisms required for endocytosis of the Bmper/Bmp4 and signaling complex and determine the mechanism of Bmper's differential effects on Bmp4 signaling. Methods and Results: Using an array of biochemical and cell biology techniques, we report that LRP1 (LDL receptor-related protein 1), a member of the LDL receptor family, acts as an endocytic receptor for Bmper and a coreceptor of Bmp4 to mediate the endocytosis of the Bmper/Bmp4 signaling complex. Furthermore, we demonstrate that LRP1-dependent Bmper/Bmp4 endocytosis is essential for Bmp4 signaling, as evidenced by the phenotype of lrp1-deficient zebrafish, which have abnormal cardiovascular development and decreased Smad1/5/8 activity in key vasculogenic structures. Conclusions: Together, these data reveal a novel role for LRP1 in the regulation of Bmp4 signaling by regulating receptor complex endocytosis. In addition, these data introduce LRP1 as a critical regulator of vascular development. These observations demonstrate Bmper's ability to fine-tune Bmp4 signaling at the single-cell level, unlike the spatial regulatory mechanisms applied by other Bmp modulators.
    Keywords: Angiogenesis, Cell signalling/signal transduction, Other Vascular biology
    Print ISSN: 0009-7330
    Electronic ISSN: 1524-4571
    Topics: Medicine
    Published by American Heart Association (AHA)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 9
    facet.materialart.
    Unknown
    Fine-tuning of FOXO3A in cHL as a survival mechanism and a hallmark of abortive plasma cell differentiation (2018)
    American Society of Hematology (ASH)
    In: Blood
    Details
    Publication Date: 2018-04-06
    Description: We recently found that FOXO1 repression contributes to the oncogenic program of classical Hodgkin lymphoma (cHL). Interestingly, FOXO3A, another member of the FOXO family, was reported to be expressed in the malignant Hodgkin and Reed-Sternberg cells of cHL at higher levels than in non-Hodgkin lymphoma subtypes. We thus aimed to investigate mechanisms responsible for the maintenance of FOXO3A as well as the potential role of FOXO3A in cHL. Here, we show that high FOXO3A levels in cHL reflect a B-cell-differentiation–specific pattern. In B cells, FOXO3A expression increases during the process of centroblast to plasma cell (PC) differentiation. FOXO3A levels in cHL were found higher than in germinal center B cells, but lower than in terminally differentiated PCs. This intermediate FOXO3A expression in cHL might manifest the "abortive PC differentiation" phenotype. This assumption was further corroborated by the finding that overexpression of FOXO3A in cHL cell lines induced activation of the master PC transcription factor PRDM1α. As factors attenuating FOXO3A expression in cHL, we identified MIR155 and constitutive activation of extracellular signal-regulated kinase. Finally, we demonstrate the importance of FOXO3A expression in cHL using an RNA interference approach. We conclude that tightly regulated expression of FOXO3A contributes to the oncogenic program and to the specific phenotype of cHL.
    Keywords: Lymphoid Neoplasia
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology (ASH)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
  • 10
    facet.materialart.
    Unknown
    Critical Roles of STAT3 in {beta}-Adrenergic Functions in the Heart [Molecular Cardiology] (2015)
    American Heart Association (AHA)
    Details
    Publication Date: 2015-12-31
    Description: Background— β-Adrenergic receptors (βARs) play paradoxical roles in the heart. On one hand, βARs augment cardiac performance to fulfill the physiological demands, but on the other hand, prolonged activations of βARs exert deleterious effects that result in heart failure. The signal transducer and activator of transcription 3 (STAT3) plays a dynamic role in integrating multiple cytokine signaling pathways in a number of tissues. Altered activation of STAT3 has been observed in failing hearts in both human patients and animal models. Our objective is to determine the potential regulatory roles of STAT3 in cardiac βAR-mediated signaling and function. Methods and Results— We observed that STAT3 can be directly activated in cardiomyocytes by β-adrenergic agonists. To follow up this finding, we analyzed βAR function in cardiomyocyte-restricted STAT3 knockouts and discovered that the conditional loss of STAT3 in cardiomyocytes markedly reduced the cardiac contractile response to acute βAR stimulation, and caused disengagement of calcium coupling and muscle contraction. Under chronic β-adrenergic stimulation, Stat3cKO hearts exhibited pronounced cardiomyocyte hypertrophy, cell death, and subsequent cardiac fibrosis. Biochemical and genetic data supported that Gα s and Src kinases are required for βAR-mediated activation of STAT3. Finally, we demonstrated that STAT3 transcriptionally regulates several key components of βAR pathway, including β 1 AR, protein kinase A, and T-type Ca 2+ channels. Conclusions— Our data demonstrate for the first time that STAT3 has a fundamental role in βAR signaling and functions in the heart. STAT3 serves as a critical transcriptional regulator for βAR-mediated cardiac stress adaption, pathological remodeling, and heart failure.
    Keywords: Animal Models of Human Disease, Cell Signaling/Signal Transduction, Genetically Altered and Transgenic Models, Congenital Heart Disease
    Electronic ISSN: 1524-4539
    Topics: Medicine
    Published by American Heart Association (AHA)
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    PAPER CURRENT
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...