Publications by authors named "Stefan Pfaffenberger"

The role of uPA in tissue remodeling and cell migration is already well established. In addition, uPA was reported to stabilize p53, a key cell cycle control, DNA repair and apoptosis initiation protein. We aimed to determine the role of uPA-uPAR signaling towards cell survival or apoptosis in human adult cardiac myocytes (HACM).

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Background: Duchenne muscular dystrophy (DMD) is an X-linked recessive disease that occurs in males leading to immobility and death in early adulthood. Female carriers of DMD are generally asymptomatic, yet frequently develop dilated cardiomyopathy. This study aims to detect early cardiac manifestation in DMD using cardiovascular magnetic resonance (CMR) and to evaluate its association with clinical symptoms.

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Objectives: The purpose of this study was to prospectively investigate the diagnostic and prognostic impact of cardiac magnetic resonance (CMR) T1 mapping and validate it against left ventricular biopsies.

Background: Extracellular volume (ECV) expansion is a key feature of heart failure. CMR T1 mapping has been developed as a noninvasive technique to estimate ECV; however, the diagnostic and prognostic impacts of this technique have not been well established.

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Aims: Recent data indicate that right ventricular systolic dysfunction (RVSD) by cardiac magnetic resonance imaging (CMR) is a strong predictor of outcome in heart failure. However, the prognostic significance of RVSD by CMR in heart failure with preserved ejection fraction (HFpEF) is unknown.

Methods And Results: We prospectively enrolled 171 HFpEF patients who underwent CMR in addition to invasive and non-invasive testing.

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Background: Previous work indicates that dilatation of the pulmonary artery (PA) itself or in relation to the ascending aorta (PA:Ao ratio) predicts pulmonary hypertension (PH). Whether these results also apply for heart failure with preserved ejection fraction (HFpEF) is unknown. In the present study we evaluated the diagnostic and prognostic power of PA diameter and PA:Ao ratio on top of right ventricular (RV) size, function, and septomarginal trabeculation (SMT) thickness by cardiovascular magnetic resonance (CMR) in HFpEF.

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Background: Lipoprotein(a) (Lp(a)) is a proatherogenic plasma lipoprotein currently established as an independent risk factor for the development of atherosclerotic disease and as a predictor for acute thrombotic complications. In addition, Lp(a) is the major carrier of proinflammatory oxidized phospholipids (OxPL). Today, atherosclerosis is considered to be an inflammatory disease of the vessel wall in which monocytes and monocyte-derived macrophages are crucially involved.

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Objective: Atherosclerosis is considered to be an inflammatory disease in which monocytes and monocyte-derived macrophages play a key role. Circulating monocytes can be divided into three distinct subtypes, namely in classical monocytes (CM; CD14++CD16-), intermediate monocytes (IM; CD14++CD16+) and non-classical monocytes (NCM; CD14+CD16++). Low density lipoprotein particles are heterogeneous in size and density, with small, dense LDL (sdLDL) crucially implicated in atherogenesis.

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Objective: High-density lipoprotein (HDL) particles are heterogeneous in structure and function and the role of HDL subfractions in atherogenesis is not well understood. It has been suggested that small HDL may be dysfunctional in patients with coronary artery disease (CAD). Monocytes are considered to play a key role in atherosclerotic diseases.

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Background: The underlying pathophysiology of heart failure with preserved ejection fraction (HFPEF) is incompletely understood, but myocardial extracellular matrix accumulation is thought to play a major role. Our aims were to estimate myocardial extracellular matrix using cardiac magnetic resonance T1 mapping and to assess the relationship between pathobiology/pathophysiology and prognosis.

Methods And Results: Patients with suspected HFPEF (n=100) were enrolled in this prospective, observational study.

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Background: Therapeutic decisions in cardiology are determined frequently by cardiac chamber size. To decide whether cardiac dimensions are still in the normal range, reliable reference values are needed. However, published reference values mostly refer to historical cohorts using motion-mode measurements and have not been adjusted for sex or age.

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Interleukin-33 (IL-33) is a recently described member of the IL-1 family of cytokines, which was identified as a ligand for the ST2 receptor. Components of the IL-33/ST2 system were shown to be expressed in normal and pressure overloaded human myocardium, and soluble ST2 (sST2) has emerged as a prognostic biomarker in myocardial infarction and heart failure. However, expression and regulation of IL-33 in human adult cardiac myocytes and fibroblasts was not tested before.

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Background: Hereditary amyloidosis with predominant renal disease can be caused by mutations in the gene encoding the fibrinogen Aα-chain (AFib). Here, we describe the clinical course of AFib amyloidosis associated with the rare R554L mutation, and the significance of extrarenal amyloid deposits and their possible influence on cardiovascular morbidity.

Methods: We report on 101 members of a family after having conducted patient interviews, chart review, genetic testing, renal biopsies and assessment for extrarenal amyloid deposition.

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Objective: Interleukin (IL)-33 is the most recently described member of the IL-1 family of cytokines and it is a ligand of the ST2 receptor. While the effects of IL-33 on the immune system have been extensively studied, the properties of this cytokine in the cardiovascular system are much less investigated. Methods/Results- We show here that IL-33 promoted the adhesion of human leukocytes to monolayers of human endothelial cells and robustly increased vascular cell adhesion molecule-1, intercellular adhesion molecule-1, endothelial selectin, and monocyte chemoattractant protein-1 protein production and mRNA expression in human coronary artery and human umbilical vein endothelial cells in vitro as well as in human explanted atherosclerotic plaques ex vivo.

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The pleiotropic cytokine oncostatin M (OSM), a member of the glycoprotein (gp)130 ligand family, plays a key role in inflammation and cardiovascular disease. As inflammation precedes and accompanies pathological angiogenesis, we investigated the effect of OSM and other gp130 ligands on vascular endothelial growth factor (VEGF) production in human vascular smooth muscle cells (SMC). Human coronary artery SMC (HCASMC) and human aortic SMC (HASMC) were treated with different gp130 ligands.

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Cardiac diseases such as myocardial infarction and heart failure are among the leading causes of death in western societies. Therapeutic angiogenesis has been suggested as a concept to combat these diseases. The biology of angiogenic factors expressed in the heart such as vascular endothelial growth factor (VEGF) is well studied, whereas data on anti-angiogenic mediators in the heart are scarce.

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Pulmonary veins (PV) display a variety of anomalies with a common trunk of the inferior pulmonary veins being the most infrequent. We report on a 65-year-old man who underwent an ablation procedure for atrial fibrillation (AF) exclusively based on electro-anatomical mapping. After recurrence of AF, a common trunk of the inferior PV was detected by computed tomography imaging resulting in a modified ablation approach.

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Plasminogen activator inhibitor-1 (PAI-1) plays a pivotal role in the regulation of the fibrinolytic system and in the modulation of extracellular proteolysis. Increased PAI-1 was found in atherosclerotic lesions, and high PAI-1 plasma levels were associated with coronary heart disease. Smooth muscle cells (SMC) are a major source of PAI-1 within the vascular wall, and PAI-1 was implicated in SMC migration, proliferation, and apoptosis.

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The chemokine MCP-1 is thought to play a key role - among many other pathophysiological processes - in myocardial infarction. MCP-1 is not only a key attractant for monocytes and macrophages and as such responsible for inflammation but might also be directly involved in the modulation of repair processes in the heart. We show that cultured human cardiac cells express MCP-1 and that its expression is upregulated by inflammatory cytokines and downregulated by hypoxia.

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In most studies showing cardio- and vasculoprotective effects of estrogens, 17beta-estradiol was used and little information on possible effects of different estrogen metabolites is yet available. We investigated whether particular estrogen metabolites are effective in counteracting inflammatory activation of human endothelium. Human endothelial cells were incubated with 17alpha-dihydroequilenin, 17beta-dihydroequilenin, delta-8,9-dehydroestrone, estrone and 17beta-estradiol and stimulated with interleukin (IL)-1alpha.

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Recent findings have implicated hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors or statins, an established class of drugs for the treatment of hypercholesterolemia, in tissue remodeling in the heart. Statins induce apoptosis in different cell culture systems including rat neonatal cardiomyocytes. We investigated possible effects of different statins in vitro in human adult cardiac myocytes on the expression of proteins thought to be involved in the regulation of apoptosis such as Mcl-1, an inhibitor of apoptosis, Bax, an inducer of apoptosis, as well as on cytoplasmic histone-associated-DNA-fragments.

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Cardiovascular diseases are a major cause of mortality in the developed world. Efficacy of thrombolysis plays an important role in the management of acute myocardial infarction and cerebral insult both in the acute event and in the long-term outcome of these patients. New adjunctive strategies have been tested, therefore, to make thrombolytic therapies more effective and safer.

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Background And Purpose: Recently, 3 clinical trials revealed encouraging results in recanalization and clinical outcome in acute stroke patients when 2-MHz transcranial Doppler monitoring was applied. This study investigated whether a 1.8-MHz commercial diagnostic ultrasound device has the potential to facilitate thrombolysis using an in vitro stroke model.

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