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  • 1
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    Diabetes insipidus and, partially, low anxiety‐related behaviour are linked to a SNP‐associated vasopressin deficit in LAB mice
    Wiley ; 2007
    In:  European Journal of Neuroscience Vol. 26, No. 10 ( 2007-11), p. 2857-2864
    Details
    In: European Journal of Neuroscience, Wiley, Vol. 26, No. 10 ( 2007-11), p. 2857-2864
    Abstract: Following secretion from the posterior pituitary, the neuropeptide vasopressin (AVP) stimulates the kidney to retain water, and when released centrally it can contribute to anxiety‐ and depression‐like behaviours. We hypothesized that CD1 mice bred for low trait anxiety (LAB) suffer from a deficit in AVP. Both osmotically stimulated peripheral secretion and intra‐paraventricular nucleus (PVN) release of AVP were found decreased in LAB animals compared with normal anxiety (NAB) or high anxiety (HAB) controls. Consequently, in addition to their extreme non‐anxiety, LAB mice showed signs of central diabetes insipidus (cDI), including increased fluid intake and reduced urine osmolality, as well as a pathological increase in plasma osmolality upon water deprivation. These cDI symptoms were attenuated by administration of a selective AVP V2 receptor agonist. A single nucleotide polymorphism (SNP) in exon 1 (C(+ 40)T) of the Avp gene of LAB animals causes an amino acid substitution in the signal peptide of the AVP precursor, and is likely to impair processing and trafficking of the precursor, as suggested by reduced axonal transport of AVP from the hypothalamic PVN, finally contributing to cDI symptoms and low trait anxiety. In an F2 panel, this SNP co‐segregated with fluid intake and showed a partial contribution to low anxiety‐related behaviour, indicated by its co‐segregation with time spent on the open arms of the elevated plus‐maze in a subset of F2 mice. Thus, the SNP‐associated deficit in plasma and central AVP contributes to signs of cDI and, at least partially, to low trait anxiety, both features being typical of LAB animals.
    Type of Medium: Online Resource
    ISSN: 0953-816X , 1460-9568
    URL: Issue
    URL: Article
    DOI: 10.1111/ejn.2007.26.issue-10
    DOI: 10.1111/j.1460-9568.2007.05917.x
    Language: English
    Publisher: Wiley
    Publication Date: 2007
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  • 2
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    Impact of atrial rhythm on pulmonary vein signals in cryoballoon ablation – Sinus rhythm predicts real-time observation of pulmonary vein isolation
    Elsevier BV ; 2019
    In:  IJC Heart & Vasculature Vol. 23 ( 2019-06), p. 100353-
    Details
    In: IJC Heart & Vasculature, Elsevier BV, Vol. 23 ( 2019-06), p. 100353-
    Type of Medium: Online Resource
    ISSN: 2352-9067
    URL: Article
    DOI: 10.1016/j.ijcha.2019.100353
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
    detail.hit.zdb_id: 2818464-6
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  • 3
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    Atrial fibrillation ablation in heart failure patients: improved systolic function after cryoballoon pulmonary vein isolation
    Wiley ; 2020
    In:  ESC Heart Failure Vol. 7, No. 5 ( 2020-10), p. 2258-2267
    Details
    In: ESC Heart Failure, Wiley, Vol. 7, No. 5 ( 2020-10), p. 2258-2267
    Abstract: Atrial fibrillation (AF) and heart failure (HF) are the most common cardiac diseases and often coexist leading to increased mortality and morbidity compared with AF patients without HF. As shown previously, AF ablation using radio frequency (RF) in HF patients leads to a reduction of AF burden, an increase of left ventricular ejection fraction (LVEF) and consequently to reduced hospitalization and mortality. Previous AF ablation studies on HF patients have been liberal about additional targets beyond pulmonary vein isolation (PVI). Thus, the aim of this study was to assess systematically the impact of a straightforward PVI‐only strategy on LVEF, NYHA functional class, and cardiovascular hospitalization rate in HF patients. Methods and results Out of 414 consecutive patients undergoing PVI, only with the cryoballoon 113 patients with reduced LVEF [mean: 38.4 ± 10.8%, reduced ejection fraction (rEF) group] and 301 patients with normal LVEF ( 〉 55%) at baseline were identified [normal ejection fraction (nEF) group]. Remarkably, even though freedom from arrhythmia recurrence after 1 year was significantly lower in the rEF group (64.9%) compared with the nEF group (71.2%, P  = 0.036), mean LVEF improved from 38.4 ± 10.8% to 52.5 ± 17.2% ( P   〈  0.001) after cryoballoon ablation in the rEF group. Accordingly, HF‐related symptoms as well as hospitalization rate declined significantly in the rEF group during follow‐up compared with baseline. Conclusions The results of the present study suggest that catheter ablation restricted to a straightforward PVI‐only strategy using the cryoballoon leads to improved left ventricular ejection fraction as well as improvement of NYHA functional class and increased freedom from cardiovascular rehospitalization.
    Type of Medium: Online Resource
    ISSN: 2055-5822 , 2055-5822
    URL: Issue
    URL: Article
    DOI: 10.1002/ehf2.v7.5
    DOI: 10.1002/ehf2.12735
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2814355-3
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  • 4
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    Datasheet1.docx
    Frontiers Media SA ; 2023
    In:  Frontiers in Cardiovascular Medicine Vol. 10 ( 2023-6-23)
    Details
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 10 ( 2023-6-23)
    Abstract: Mitral annular alterations in the context of heart failure often lead to severe functional mitral regurgitation (FMR), which should be treated with transcatheter edge-to-edge repair (M-TEER) according to current guidelines. M-TEER's effects on mitral valve (MV) annular remodeling have not been well elucidated. Methods 141 consecutive patients undergoing M-TEER for treatment of FMR were included in this investigation. Comprehensive intraprocedural transesophageal echocardiography was used to assess the acute effects of M-TEER on annular geometry. Results Average patient age was 76.2 ± 9.6 years and 46.1% were female patients. LV ejection fraction was reduced (37.0% ± 13.7%) and all patients had mitral regurgitation (MR) grade ≥III. M-TEER achieved optimal MR reduction (MR ≤ I) in 78.6% of patients. Mitral annular anterior-posterior diameters (A-Pd) were reduced by −6.2% ± 9.5% on average, whereas anterolateral-posteromedial diameters increased (3.7% ± 8.9%). Overall, a reduction in MV annular areas was observed (2D: −1.8% ± 13.1%; 3D: −2.7% ± 13.7%), which strongly correlated with A-Pd reduction (2D: r  = 0.6, p   & lt; 0.01; 3D: r  = 0.65, p   & lt; 0.01). Patients that achieved A-Pd reduction above the median (≥6.3%) showed significantly lower rates of the composite endpoint rehospitalization for heart failure or all-cause mortality than those with less A-Pd reduction (9.9% vs. 28.6%, p  = 0.037, log-rank p  = 0.039). Furthermore, patients reaching the composite endpoint had an increase in annular area (2D: 3.0% ± 15.4%; 3D: 1.9% ± 15.3%), whereas those not reaching the endpoint showed a decrease (2D: −2.7% ± 12.4%; 3D: −3.6% ± 13.3%), although residual MR after M-TEER was similar between these groups ( p  = 0.57). In multivariate Cox regression adjusted for baseline MR, A-Pd reduction ≥6.3% remained a significant predictor of the combined endpoint (OR: 0.35, 95% CI: 0.14–0.85, p  = 0.02). Conclusion Our findings indicate that effects of M-TEER in FMR are not limited to MR reduction, but also have significant impact on annular geometry. Moreover, A-Pd reduction, which mediates annular remodeling, has a significant impact on clinical outcome independent of residual MR.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    URL: Article
    URL: Article
    DOI: 10.3389/fcvm.2023.1143702
    DOI: 10.3389/fcvm.2023.1143702.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2781496-8
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  • 5
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    Trends in Transcatheter Edge-to-Edge Mitral Valve Repair Over a Decade: Data From the MiTra ULM Registry
    Frontiers Media SA ; 2022
    In:  Frontiers in Cardiovascular Medicine Vol. 9 ( 2022-3-8)
    Details
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2022-3-8)
    Abstract: This study sought to determine the potential change in trends in the baseline characteristics of patients with symptomatic severe mitral regurgitation who underwent transcatheter edge-to-edge mitral valve repair (M-TEER) over the last decade in a high-volume center. Methodology The investigation included 942 symptomatic patients with moderate-to-severe and severe mitral regurgitation who underwent transcatheter edge-to-edge repair (TEER) at our institution between January 2010 and March 2021. Patients were divided into quintiles and compared separately. Results Patients treated in the last quintile had significantly lower surgical risk (Euro Score 7.2 ± 6.8% in the last quintile vs. 10.9 ± 9.4% in the first quintile, p & lt; 0.001), better New York Heart Association (NYHA) status (NYHA IV 14% in the last quintile vs. 40% in the first quintile, p & lt; 0.001), lower NT-pro-BNP, and smaller left ventricle diameter than patients who were treated in the first quintile. There was no difference in age between quintiles. However, an invasive hemodynamic assessment did not show significant changes over the last decade (sPAP 51.35 ± 16.2 mmHg in the first quintile vs. 51.02 ± 14.5 mmHg in the last quintile, p = 0.90, pulmonary capillary wedge V wave 30.7 ± 14.8 mmHg in the first quintile vs. 27.4 ± 10.3 mmHg in the last quintile, p = 0.40). There is a significant trend of a gradually increasing proportion of patients with degenerative mitral regurgitation (MR) over the last 10 years ( p & lt; 0.001). The experience gained in the M-TEER procedure brought a significant reduction in fluoroscopy time and hospitalization duration. Medical therapy significantly changed over the last decade in terms of higher use of angiotensin receptor blockers (ARBs), lower use of angiotensin-converting enzyme inhibitors (ACEIs), and the introduction of angiotensin receptor-neprilysin inhibitors (ARNIs). Conclusion Patients undergoing the M-TEER procedure nowadays have lower surgical risk and are treated before they develop a significant left ventricular (LV) remodeling than before. The increasing expertise on the procedure over the last decade led to a rising number of patients with complex degenerative pathology being treated.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    URL: Article
    DOI: 10.3389/fcvm.2022.850356
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2781496-8
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  • 6
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    Single-dose of adrecizumab versus placebo in acute cardiogenic shock (ACCOST-HH): an investigator-initiated, randomised, double-blinded, placebo-controlled, multicentre trial
    Elsevier BV ; 2022
    In:  The Lancet Respiratory Medicine Vol. 10, No. 3 ( 2022-03), p. 247-254
    Details
    In: The Lancet Respiratory Medicine, Elsevier BV, Vol. 10, No. 3 ( 2022-03), p. 247-254
    Type of Medium: Online Resource
    ISSN: 2213-2600
    URL: Article
    DOI: 10.1016/S2213-2600(21)00439-2
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
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  • 7
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    Ion Flux Dependent and Independent Functions of Ion Channels in the Vertebrate Heart: Lessons Learned from Zebrafish
    Hindawi Limited ; 2012
    In:  Stem Cells International Vol. 2012 ( 2012), p. 1-9
    Details
    In: Stem Cells International, Hindawi Limited, Vol. 2012 ( 2012), p. 1-9
    Abstract: Ion channels orchestrate directed flux of ions through membranes and are essential for a wide range of physiological processes including depolarization and repolarization of biomechanical activity of cells. Besides their electrophysiological functions in the heart, recent findings have demonstrated that ion channels also feature ion flux independent functions during heart development and morphogenesis. The zebrafish is a well-established animal model to decipher the genetics of cardiovascular development and disease of vertebrates. In large scale forward genetics screens, hundreds of mutant lines have been isolated with defects in cardiovascular structure and function. Detailed phenotyping of these lines and identification of the causative genetic defects revealed new insights into ion flux dependent and independent functions of various cardiac ion channels.
    Type of Medium: Online Resource
    ISSN: 1687-966X , 1687-9678
    URL: Article
    DOI: 10.1155/2012/462161
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2012
    detail.hit.zdb_id: 2573856-2
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  • 8
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    The endocrine stress response is linked to one specific locus on chromosome 3 in a mouse model based on extremes in trait anxiety
    Springer Science and Business Media LLC ; 2012
    In:  BMC Genomics Vol. 13, No. 1 ( 2012-12)
    Details
    In: BMC Genomics, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2012-12)
    Abstract: The hypothalamic-pituitary-adrenal (HPA) axis is essential to control physiological stress responses in mammals. Its dysfunction is related to several mental disorders, including anxiety and depression. The aim of this study was to identify genetic loci underlying the endocrine regulation of the HPA axis. Method High (HAB) and low (LAB) anxiety-related behaviour mice were established by selective inbreeding of outbred CD-1 mice to model extremes in trait anxiety. Additionally, HAB vs. LAB mice exhibit comorbid characteristics including a differential corticosterone response upon stress exposure. We crossbred HAB and LAB lines to create F1 and F2 offspring. To identify the contribution of the endocrine phenotypes to the total phenotypic variance, we examined multiple behavioural paradigms together with corticosterone secretion-based phenotypes in F2 mice by principal component analysis. Further, to pinpoint the genomic loci of the quantitative trait of the HPA axis stress response, we conducted genome-wide multipoint oligogenic linkage analyses based on Bayesian Markov chain Monte Carlo approach as well as parametric linkage in three-generation pedigrees, followed by a two-dimensional scan for epistasis and association analysis in freely segregating F2 mice using 267 single-nucleotide polymorphisms (SNPs), which were identified to consistently differ between HAB and LAB mice as genetic markers. Results HPA axis reactivity measurements and behavioural phenotypes were represented by independent principal components and demonstrated no correlation. Based on this finding, we identified one single quantitative trait locus (QTL) on chromosome 3 showing a very strong evidence for linkage (2ln (L-score) 〉 10, LOD 〉 23) and significant association (lowest Bonferroni adjusted p 〈 10 -28 ) to the neuroendocrine stress response. The location of the linkage peak was estimated at 42.3 cM (95% confidence interval: 41.3 - 43.3 cM) and was shown to be in epistasis (p-adjusted 〈 0.004) with the locus at 35.3 cM on the same chromosome. The QTL harbours genes involved in steroid synthesis and cardiovascular effects. Conclusion The very prominent effect on stress-induced corticosterone secretion of the genomic locus on chromosome 3 and its involvement in epistasis highlights the critical role of this specific locus in the regulation of the HPA axis.
    Type of Medium: Online Resource
    ISSN: 1471-2164
    URL: Article
    DOI: 10.1186/1471-2164-13-579
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2012
    detail.hit.zdb_id: 2041499-7
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  • 9
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    The representative COVID-19 cohort Munich (KoCo19): from the beginning of the pandemic to the Delta virus variant
    Springer Science and Business Media LLC ; 2023
    In:  BMC Infectious Diseases Vol. 23, No. 1 ( 2023-07-13)
    Details
    In: BMC Infectious Diseases, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2023-07-13)
    Abstract: Population-based serological studies allow to estimate prevalence of SARS-CoV-2 infections despite a substantial number of mild or asymptomatic disease courses. This became even more relevant for decision making after vaccination started. The KoCo19 cohort tracks the pandemic progress in the Munich general population for over two years, setting it apart in Europe. Methods Recruitment occurred during the initial pandemic wave, including 5313 participants above 13 years from private households in Munich. Four follow-ups were held at crucial times of the pandemic, with response rates of at least 70%. Participants filled questionnaires on socio-demographics and potential risk factors of infection. From Follow-up 2, information on SARS-CoV-2 vaccination was added. SARS-CoV-2 antibody status was measured using the Roche Elecsys® Anti-SARS-CoV-2 anti-N assay (indicating previous infection) and the Roche Elecsys® Anti-SARS-CoV-2 anti-S assay (indicating previous infection and/or vaccination). This allowed us to distinguish between sources of acquired antibodies. Results The SARS-CoV-2 estimated cumulative sero-prevalence increased from 1.6% (1.1-2.1%) in May 2020 to 14.5% (12.7-16.2%) in November 2021. Underreporting with respect to official numbers fluctuated with testing policies and capacities, becoming a factor of more than two during the second half of 2021. Simultaneously, the vaccination campaign against the SARS-CoV-2 virus increased the percentage of the Munich population having antibodies, with 86.8% (85.5-87.9%) having developed anti-S and/or anti-N in November 2021. Incidence rates for infections after (BTI) and without previous vaccination (INS) differed (ratio INS/BTI of 2.1, 0.7-3.6). However, the prevalence of infections was higher in the non-vaccinated population than in the vaccinated one. Considering the whole follow-up time, being born outside Germany, working in a high-risk job and living area per inhabitant were identified as risk factors for infection, while other socio-demographic and health-related variables were not. Although we obtained significant within-household clustering of SARS-CoV-2 cases, no further geospatial clustering was found. Conclusions Vaccination increased the coverage of the Munich population presenting SARS-CoV-2 antibodies, but breakthrough infections contribute to community spread. As underreporting stays relevant over time, infections can go undetected, so non-pharmaceutical measures are crucial, particularly for highly contagious strains like Omicron.
    Type of Medium: Online Resource
    ISSN: 1471-2334
    URL: Article
    DOI: 10.1186/s12879-023-08435-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2041550-3
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  • 10
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    Identification of novel downstream targets of platelet glycoprotein VI activation by differential proteome analysis: implications for thrombus formation
    American Society of Hematology ; 2010
    In:  Blood Vol. 115, No. 20 ( 2010-05-20), p. 4102-4110
    Details
    In: Blood, American Society of Hematology, Vol. 115, No. 20 ( 2010-05-20), p. 4102-4110
    Abstract: Platelets play a key role in hemostasis and various diseases including arterial thrombosis. Glycoprotein VI (GPVI) mediates adhesion to collagen structures exposed at sites of vascular injury and subsequent platelet activation. We determined the effects of specific activation of GPVI on the human platelet proteome. Isolated human platelets were stimulated with an activating monoclonal antibody specific for GPVI. Platelet proteins were analyzed by 2-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry. We identified 8 differentially abundant proteins associated with cell signaling, metabolism, organization and rearrangement of the cytoskeleton, and membrane trafficking. Differentially abundant proteins included aldose reductase (AR), beta-centractin, charged multivesicular body protein 3, Src substrate cortactin, ERp57, and pleckstrin. Importantly, GPVI-modulated protein abundance was functionally relevant. Correspondingly, AR enzyme activity significantly increased upon GPVI activation and inhibition of AR resulted in reduced platelet aggregation. Furthermore, ERp57 was released upon ligation of platelet GPVI and increased the activity of tissue factor, a major initiator of blood coagulation. In summary, GPVI activation results in differential changes in abundance of platelet proteins, including AR and ERp57, which support platelet aggregation and platelet-dependent coagulation. These results provide further insight into the mechanisms that underlie platelet activation through the GPVI receptor and may help to identify novel pharmacologic targets.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2009-07-230268
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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