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Publications (5)5.87 Total impact

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    [Show abstract] [Hide abstract] ABSTRACT: Vascular remodeling due to excessive proliferation of endothelial and smooth muscle cells is a hallmark feature of pulmonary hypertension. microRNAs (miRNAs) are a class of small, non-coding RNA fragments that have recently been associated with remodeling of pulmonary arteries, in particular by silencing the bone morphogenetic protein receptor type II (BMPR2). Here we identified a novel pathway involving the concerted action of miR-125a, BMPR2 and cyclin-dependent kinase inhibitors (CDKN) that controls a proliferative phenotype of endothelial cells. An in silico approach predicted miR-125a to target BMPR2. Functional inhibition of miR-125a resulted in increased proliferation of these cells, an effect that was found accompanied by upregulation of BMPR2 and reduced expression of the tumor suppressors CDKN1A (p21) and CDKN2A (p16). These data were confirmed in experimental pulmonary hypertension in vivo. Levels of miR-125a were elevated in lung tissue of hypoxic animals that develop pulmonary hypertension. In contrast, circulating levels of miR-125a were found to be lower in mice with pulmonary hypertension as compared to control mice. Similar findings were observed in a small cohort of patients with precapillary pulmonary hypertension. These translational data emphasize the pathogenetic role of miR-125a in pulmonary vascular remodeling. © 2015 by the Society for Experimental Biology and Medicine.
    Preview · Article · Apr 2015 · Experimental Biology and Medicine
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    Leonardo Glutz von Blotzheim · Stefan Christen · Stephan Wieser · Silvia Ulrich · Lars C Huber
    [Show abstract] [Hide abstract] ABSTRACT: We investigated the prevalence of bronchial asthma in patients with Tako-Tsubo Syndrome (TTS). This retrospective case-series study was conducted in a primary care hospital in Zurich, Switzerland. Data of all patients with newly diagnosed TTS (2002 - 2012) were assessed electronically by the use of ICD-10. Asthma prevalence was compared to published epidemiologic data. Bronchial asthma is characterized by airway inflammation and, during attack, release of endogenous catecholamines. Sympathomimetic drugs are the mainstay of treatment for asthma patients. Likewise, catecholamine mediated diffuse microvascular myocardial dysfunction seems to be of critical importance for the development of TTS. 20 cases of TTS were identified. 90% were female, showed a median age of 70±13y [25y - 90y], an apical and/or midventricular ballooning pattern with preserved basal function and a median initial LVEF of 34±9% [25% - 55%]. 65% of patients underwent coronary angiography to rule out significant coronary artery disease. Hypertension was present in 45% of patients, 35% were smokers, none was suffering from diabetes. Prevalence of asthma in patients with TTS was significantly higher compared to the normal population (25% vs. 7%, p=0.012). In 30% of the TTS patients an iatrogenic cause for development of TTS was identified. Prevalence of asthma was significantly higher in patients with TTS compared to epidemiologic data from an age-matched population. Phenotypes of patients developing obstructive ventilatory disease and TTS might share common pathogenic mechanisms beyond the use of bronchodilatators. In addition, we identified other iatrogenic etiologies in patients with TTS.
    Preview · Article · Feb 2015 · The Open Cardiovascular Medicine Journal
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    [Show abstract] [Hide abstract] ABSTRACT: Martorell hypertensive ischemic leg ulcer (Martorell ulcer) is characterized by distinct alterations in the arteriolar wall of subcutaneous vessels, leading to progressive narrowing of the vascular lumen and increase of vascular resistance. These changes are similar to the alterations observed in pulmonary arterioles in patients with chronic pulmonary hypertension (PH). This study was aimed to assess an association between the two disorders. In this case-control study, 14 patients with Martorell ulcer were clinically assessed for the presence of pulmonary hypertension using transthoracic Doppler echocardiography. Data from patients were compared to 28 matched hypertensive controls. Systolic pulmonary arterial pressure (sPAP) in patients with Martorell ulcer was significantly higher than in the control group (33.8 ± 16.9 vs 25.3 ± 6.5 mmHg, p = 0.023); the prevalence of pulmonary hypertension was 31% (5/14) in patients and 7% (2/28) in controls (p = 0.031). No differences were seen in left heart size and function between patients and controls. This study provides first evidence that subcutaneous arteriolosclerosis, the hallmark of Martorell ulcer, is associated with PH. These findings suggest that patients with Martorell leg ulcer might be at significant risk to develop elevated pulmonary arterial pressure. Patients with leg ulcers who present with dyspnea should be evaluated by echocardiography for the presence of pulmonary hypertension.
    Full-text · Article · Jun 2012 · Respiratory research
  • L. Glutz von Blotzheim · N.J. Müller · L.C. Huber · T. Degen
    [Show abstract] [Hide abstract] ABSTRACT: Wir berichten über den Fall einer 76-jährigen Patientin, die sich mit einer tiefen Beinvenenthrombose und zervikaler Lymphadenopathie präsentierte. Computertomographisch bestand der Verdacht auf multiple Lebermetastasen bei unklarem Primärtumor. Die Differenzialdiagnose von Lymphadenopathie und Leberläsionen ist breit und beinhaltet u. a. maligne Prozesse sowie verschiedene infektiöse Ursachen. Die weiterführende Diagnostik zeigte das in unseren Breiten seltene Bild einer Lymphknotentuberkulose mit multiplen hepatischen Tuberkulomen bei wiederholt negativem Interferon-γ-release-Test. Unter kombinierter 4er-Therapie kam es im Verlauf zu einer kompletten Remission.
    No preview · Article · Jun 2012 · Der Internist
  • L Glutz von Blotzheim · N J Müller · L C Huber · T Degen
    [Show abstract] [Hide abstract] ABSTRACT: We report the case of a 76-year-old female patient presenting with deep venous thrombosis and upper cervical lymphadenopathy. A computed tomography (CT) scan showed multiple hepatic lesions with a high suspicion of metastatic disease from an unknown primary tumor. The differential diagnosis of lymphadenopathy and hepatic lesions includes malignant tumors and various infectious diseases. The diagnostic process, however, revealed lymph node tuberculosis with multiple hepatic granulomas despite a repeatedly negative interferon-γ release assay. A combined antituberculosis therapy led to complete clinical remission.
    No preview · Article · Apr 2012 · Der Internist