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Kamphuisen P.W.,University of Groningen | Ten Cate H.,Cardiovascular Research Institute Maastricht | Ten Cate H.,Maastricht University
Blood | Year: 2014

Patients with hemophilia, who have a life-long hypocoagulability, seem to have a lower cardiovascular mortality than the general population. Nevertheless, the prevalence of cardiovascular risk factors in patients with hemophilia is as prevalent as in the general population, and hypertension is even more common. Furthermore, hemophiliacs have the same degree of atherosclerosis as the general population. The reduced cardiovascular mortality may be explained by reduced thrombus formation resulting from hypocoagulability. On the other hand, hemophilia, which is associated with reduced thrombin generation, may also increase atherosclerotic plaque stability, as has been shown in mice. Because treatment of these events is extremely challenging in patients with increased bleeding tendency, detection and aggressive treatment of risk factors is mandatory. © 2014 by The American Society of Hematology.


News Article | December 27, 2016
Site: www.eurekalert.org

The Biophysical Society has announced the winners of its international travel grants to attend the Biophysical Society's 61st Annual Meeting in New Orleans, February 11-15, 2017. The purpose of these awards is to foster and initiate further interaction between American biophysicists and scientists working in countries experiencing financial difficulties. Recipients of this competitive award are chosen based on scientific merit and their proposed presentation at the meeting. They will be honored at a reception on Sunday, February 12 at the Ernest N. Morial Convention Center. The 2017 recipients of the International Travel Award, along with their institutional affiliation and abstract title, are listed below. Ana F. Guedes, Institute of Molecular Medicine, Portugal, ATOMIC FORCE MICROSCOPY AS A TOOL TO EVALUATE THE RISK OF CARDIOVASCULAR DISEASES IN PATIENTS. Karishma Bhasne Mohali, Indian Institute of Science Education and Research (IISER), A TALE OF TWO AMYLOIDOGENIC INTRINSICALLY DISORDERED PROTEINS: INTERPLAY OF TAU AND α-SYNUCLEIN. Chan Cao, East China University of Science and Technology, DIRECT IDENTIFICATION OF ADENINE, THYMINE, CYTOSINE AND GUANINE USING AEROLYSIN NANOPORE. Venkata Reddy Chirasani, Indian Institute of Technology Madras, LIPID TRANSFER MECHANISM OF CETP BETWEEN HDL AND LDL: A COARSEGRAINED SIMULATION STUDY. Assaf Elazar, Weizmann Institute of Science, Israel, DECIPHERING MEMBRANE PROTEIN ENERGETICS USING DEEP SEQUENCING; TOWARDS ROBUST DESIGN AND STRUCTURE PREDICTION OF MEMBRANE PROTEINS. Manuela Gabriel, University of Buenos Aires, Argentina, 3D ORBITAL TRACKING OF SINGLE GOLD NANOPARTICLES: A NEW APPROACH TO STUDY VESICLE TRAFFICKING IN CHROMAFFIN CELLS. Farah Haque National Centre for Biological Sciences, India, A NEW HUMANIZED MOUSE MODEL FOR STUDYING INHERITED CARDIOMYOPATHIC MUTATIONS IN THE MYH7 GENE. Stephanie Heusser, Stockholm University, Switzerland, STRUCTURAL AND FUNCTIONAL EVIDENCE FOR MULTI-SITE ALLOSTERY MEDIATED BY GENERAL ANESTHETICS IN A MODEL LIGAND-GATED ION CHANNEL. Amir Irani, Massey University, New Zealand, HOMOGALACTURONANS ILLUMINATE THE ROLE OF COUNTERION CONDENSATION IN POLYELECTROLYTE TRANSPORT. Olfat Malak, University of Nantes, France, HIV-TAT INDUCES A DECREASE IN IKR AND IKS VIA REDUCTION IN PHOSPHATIDYLINOSITOL-(4,5)-BISPHOSPHATE AVAILABILITY. CONFORMATIONAL TRANSITION AND ASSEMBLY OF E.COLI CYTOLYSIN A PORE FORMING TOXIN BY SINGLE MOLECULE FLUORESCENCE. Sabrina Sharmin, Shizuoka University, Japan, EFFECTS OF LIPID COMPOSITIONS ON THE ENTRY OF CELL PENETRATING PEPTIDE OLIGOARGININE INTO SINGLE VESICLES. Xin Shi, East China University of Science and Technology, DIRECT OBSERVATION OF SINGLE BIOPOLYMER FOLDING AND UNFOLDING PROCESS BY SOLIDSTATE NANOPORE. Omar Alijevic, University of Lausanne, Switzerland, ANALYSIS OF GATING OF ACID-SENSING ION CHANNELS (ASICS) UNDER RAPID AND SLOW PH CHANGES. Swapna Bera, Bose Institute, India, BIOPHYSICAL INSIGHTS INTO THE MEMBRANE INTERACTION OF THE CORE AMYLOID-FORMING Aβ40 FRAGMENT K16-K28 AND ITS ROLE IN THE PATHOGENESIS OF ALZHEIMER'S DISEASE. Anais Cassaignau, University College London, United Kingdom, STRUCTURAL INVESTIGATION OF AN IMMUNOGLOBULIN DOMAIN ON THE RIBOSOME USING NMR SPECTROSCOPY. Bappaditya Chandra, Tata Institute of Fundamental Research, India, SECONDARY STRUCTURE FLIPPING CONNECTED TO SALT-BRIDGE FORMATION CONVERTS TOXIC AMYLOID-β40 OLIGOMERS TO FIBRILS. Gayathri Narasimhan, Cinvestav, Mexico, ANTIHYPERTROPHIC EFFECTS OF DIAZOXIDE INVOLVES CHANGES IN MIR-132 EXPRESSION IN ADULT RAT CARDIOMYCYTES. Giulia Paci, European Molecular Biology Laboratory, Germany, FOLLOWING A GIANT'S FOOTSTEPS: SINGLE-PARTICLE AND SUPER-RESOLUTION APPROACHES TO DECIPHER THE NUCLEAR TRANSPORT OF HEPATITIS B VIRUS CAPSIDS. Bizhan Sharopov, Bogomoletz Institute of Physiology National Academy of Sciences of Ukraine, DISSECTING LOCAL AND SYSTEMIC EFFECTS OF TRPV1 ON BLADDER CONTRACTILITY IN DIABETES. Chao Sun, East China Normal University, FUNCTION OF BACTERIORUBERIN IN ARCHAERHODOPSIN 4, FROM EXPRESSION TO CHARACTERIZATION. Matthew Batchelor, University of Leeds, United Kingdom STRUCTURAL DYNAMICS IN THE MYOSIN 7A SINGLE α-HELIX DOMAIN. Daniel Havelka, Czech Academy of Sciences, MICROVOLUME DIELECTRIC SPECTROSCOPY AND MOLECULAR DYNAMICS OF AMINO ACIDS. Ivan Kadurin, University College London, United Kingdom, INVESTIGATION OF THE PROTEOLYTIC CLEAVAGE OF α2δ SUBUNITS: A MECHANISTIC SWITCH FROM NHIBITION TO ACTIVATION OF VOLTAGE-GATED CALCIUM CHANNELS? Linlin Ma, University of Queensland, Australia, NOVEL HUMAN EAG CHANNEL ANTAGONISTS FROM SPIDER VENOMS. Ivana Malvacio, University of Cagliari, Italy, MOLECULAR INSIGHTS ON THE RECOGNITION OF SUBSTRATES BY THE PROMISCUOUS EFFLUX PUMP ACRB. Cristina Moreno Vadillo, Cardiovascular Research Institute Maastricht, Netherlands, RESTORING DEFECTIVE CAMP-DEPENDENT UPREGULATION IN LONG-QT SYNDROME TYPE-1 THROUGH INTERVENTIONS THAT PROMOTE IKS CHANNEL OPENING. Melanie Paillard, Claude Bernard University Lyon 1, France, TISSUE-SPECIFIC MITOCHONDRIAL DECODING OF CYTOPLASMIC CA2+ SIGNALS IS CONTROLLED BY THE STOICHIOMETRY OF MICU1/2 AND MCU. Mohammed Mostafizur Rahman, Institute for Stem Cell Biology and Regenerative Medicine, India, STRESS-INDUCED DIFFERENTIAL REGULATION LEADS TO DECOUPLING OF THE ACTIVITY BETWEEN MPFC AND AMYGDALA. Marcin Wolny, University of Leeds, United Kingdom, DESIGN AND CHARACTERIZATION OF LONG AND STABLE DE NOVO SINGLE α-HELIX DOMAINS. Elvis Pandzic, University of New South Wales, Australia, VELOCITY LANDSCAPES RESOLVE MULTIPLE DYNAMICAL POPULATIONS FROM FLUORESCENCE IMAGE TIME SERIES. The Biophysical Society, founded in 1958, is a professional, scientific Society established to encourage development and dissemination of knowledge in biophysics. The Society promotes growth in this expanding field through its annual meeting, monthly journal, and committee and outreach activities. Its 9000 members are located throughout the U.S. and the world, where they teach and conduct research in colleges, universities, laboratories, government agencies, and industry. For more information on these awards, the Society, or the 2017 Annual Meeting, visit http://www.


Scheijen J.L.J.M.,Maastricht University | Schalkwijk C.G.,Maastricht University | Schalkwijk C.G.,Cardiovascular Research Institute Maastricht
Clinical Chemistry and Laboratory Medicine | Year: 2014

Background: The reactive α-oxoaldehydes glyoxal (GO), methylglyoxal (MGO) and 3-deoxyglucosone (3-DG) have been linked to diabetic complications and other age-related diseases. Numerous techniques have been described for the quantification of á-oxoaldehydes in blood or plasma, although with several shortcomings such as the need of large sample volume, elaborate extraction steps or long run-times during analysis. Therefore, we developed and evaluated an improved method including sample preparation, for the quantification of these α-oxoaldehydes in blood and plasma with ultra performance liquid chromatography tandem mass spectrometry (UPLC MS/MS). Methods: EDTA plasma and whole blood samples were deproteinized using perchloric acid (PCA) and subsequently derivatized with o-phenylenediamine (oPD). GO, MGO and 3-DG concentrations were determined using stable isotope dilution UPLC MS/MS with a run-to-run time of 8 min. Stability of α-oxoaldehyde concentrations in plasma and whole blood during storage was tested. The concentration of GO, MGO and 3-DG was measured in EDTA plasma of non-diabetic controls and patients with type 2 diabetes (T2DM). Results: Calibration curves of GO, MGO and 3-DG were linear throughout selected ranges. Recoveries of these α-oxoaldehydes were between 95% and 104%. Intra-and inter-assay CVs were between 2% and 14%. Conclusions: To obtain stable and reliable α-oxoaldehyde concentrations, immediate centrifugation of blood after blood sampling is essential and the use of EDTA as anticoagulant is preferable. Moreover, immediate precipitation of plasma protein with PCA stabilized α-oxoaldehyde concentrations for at least 120 min. With the use of the developed method, we found increased plasma concentrations of GO, MGO and 3-DG in T2DM as compared with non-diabetic controls. © 2014 by Walter de Gruyter Berlin Boston.


Linz D.,Universitatsklinikum des Saarlandes | Mahfoud F.,Universitatsklinikum des Saarlandes | Schotten U.,Cardiovascular Research Institute Maastricht | Ukena C.,Universitatsklinikum des Saarlandes | And 3 more authors.
Hypertension | Year: 2012

The aim of this study was to identify the relative impact of adrenergic and cholinergic activity on atrial fibrillation (AF) inducibility and blood pressure (BP) in a model for obstructive sleep apnea. Obstructive sleep apnea is associated with sympathovagal disbalance, AF, and postapneic BP rises. Renal denervation (RDN) reduces renal efferent and possibly also afferent sympathetic activity and BP in resistant hypertension. The effects of RDN compared with β-blockade by atenolol on atrial electrophysiological changes, AF inducibility, and BP during obstructive events and on shortening of atrial effective refractory period (AERP) induced by high-frequency stimulation of ganglionated plexi were investigated in 20 anesthetized pigs. Tracheal occlusion with applied negative tracheal pressure (NTP; at -80 mbar) induced pronounced AERP shortening and increased AF inducibility in all of the pigs. RDN but not atenolol reduced NTP-induced AF-inducibility (20% versus 100% at baseline; P=0.0001) and attenuated NTP-induced AERP shortening more than atenolol (27 ±5 versus 43 ±3 ms after atenolol; P=0.0272). Administration of atropine after RDN or atenolol completely inhibited NTP-induced AERP shortening. AERP shortening induced by highfrequency stimulation of ganglionated plexi was not influenced by RDN, suggesting that changes in sensitivity of ganglionated plexi do not play a role in the antiarrhythmic effect of RDN. Postapneic BP rise was inhibited by RDN and not modified by atenolol. We showed that vagally mediated NTP-induced AERP shortening is modulated by RDN or atenolol, which emphasizes the importance of autonomic disbalance in obstructive sleep apnea-associated AF. Renal denervation displays antiarrhythmic effects by reducing NTP-induced AERP shortening and inhibits postapneic BP rises associated with obstructive events. © 2012 American Heart Association, Inc.


Kubben N.,Cardiovascular Research Institute Maastricht
Nucleus (Austin, Tex.) | Year: 2010

The nuclear lamina is an interconnected meshwork of intermediate filament proteins underlying the nuclear envelope. The lamina is an important regulator of nuclear structural integrity as well as nuclear processes, including transcription, DNA replication and chromatin remodeling. The major components of the lamina are A- and B-type lamins. Mutations in lamins impair lamina functions and cause a set of highly tissue-specific diseases collectively referred to as laminopathies. The phenotypic diversity amongst laminopathies is hypothesized to be caused by mutations affecting specific protein interactions, possibly in a tissue-specific manner. Current technologies to identify interaction partners of lamin A and its mutants are hampered by the insoluble nature of lamina components. To overcome the limitations of current technologies, we developed and applied a novel, unbiased approach to identify lamin A-interacting proteins. This approach involves expression of the high-affinity OneSTrEP-tag, precipitation of lamin-protein complexes after reversible protein cross-linking and subsequent protein identification by mass spectrometry. We used this approach to identify in mouse embryonic fibroblasts and cardiac myocyte NklTAg cell lines proteins that interact with lamin A and its mutant isoform progerin, which causes the premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS). We identified a total of 313 lamina-interacting proteins, including several novel lamin A interactors, and we characterize a set of 35 proteins which preferentially interact with lamin A or progerin.


Prinzen F.W.,Cardiovascular Research Institute Maastricht | Auricchio A.,Fondazione Cardiocentro Ticino
Journal of Cardiovascular Translational Research | Year: 2012

The hemodynamic, mechanical and electrical effects of cardiac resynchronization therapy (CRT) occur immediate and are lasting as long as CRT is delivered. Therefore, it is reasonable to assume that acute hemodynamic effects should predict long-term outcome. However, in the literature there is more evidence against than in favour of this idea. This raises the question of what factor(s) do relate to the benefit of CRT. There is increasing evidence that dyssynchrony, presumably through the resultant abnormal local mechanical behaviour, induces extensive remodelling, comprising structure, as well as electrophysiological and contractile processes. Resynchronization has been shown to reverse these processes, even in cases of limited hemodynamic improvement. These data may indicate the need for a paradigm shift in order to achieve maximal long-term CRT response. © The Author(s) 2011.


Auricchio A.,Fondazione Cardiocentro Ticino | Prinzen F.W.,Cardiovascular Research Institute Maastricht
Circulation Journal | Year: 2011

A variable proportion of cardiac resynchronization therapy (CRT) patients do not benefit from treatment (termed 'non-responders'). The problem of non-response to CRT might become increasingly important, because it is anticipated that larger groups of heart failure patients are indicated to the therapy. This article will discuss the definition of response to CRT, the parameters related to response to CRT, and finally whether response to CRT might be predicted. The effort to improve patient selection in order to maximize human and financial resource utilization has fallen short so far. It is, however, conceivable that rather than the identification of a 'universally' applicable cut-off value, risk strata - in which inclusion of method for determination of left ventricular volumes, etiology, QRS duration and morphology, etc - might better serve the goal of defining non-responders. Potentially simple clinical scores might help in refining outcome and by doing so, allow to more precisely measure response to CRT in daily practice in the individual patient at the time of CRT implantation. Although sophisticated cardiac imaging modalities have been intensively utilized for improving patient outcome, it seems that many mechanical dyssynchrony measures suffer from technical limitations and from difficult interpretation of the complex signals, which lack reproducibility outside highly specialized laboratories.


Chatrou M.L.L.,Cardiovascular Research Institute Maastricht | Winckers K.,Cardiovascular Research Institute Maastricht | Hackeng T.M.,Cardiovascular Research Institute Maastricht | Reutelingsperger C.P.,Cardiovascular Research Institute Maastricht | Schurgers L.J.,Cardiovascular Research Institute Maastricht
Blood Reviews | Year: 2012

Vitamin K-antagonists (VKA) are the most widely used anti-thrombotic drugs with substantial efficacy in reducing risk of arterial and venous thrombosis. Several lines of evidence indicate, however, that VKA inhibit not only post-translational activation of vitamin K-dependent coagulation factors but also synthesis of functional extra-hepatic vitamin K-dependent proteins thereby eliciting undesired side-effects. Vascular calcification is one of the recently revealed side-effects of VKA. Vascular calcification is an actively regulated process involving vascular cells and a number of vitamin K-dependent proteins. Mechanistic understanding of vascular calcification is essential to improve VKA-based treatments of both thrombotic disorders and atherosclerosis. This review addresses vitamin K-cycle and vitamin K-dependent processes of vascular calcification that are affected by VKA. We conclude that there is a growing need for better understanding of the effects of anticoagulants on vascular calcification and atherosclerosis. © 2012 Elsevier Ltd.


Wellens H.J.,Cardiovascular Research Institute Maastricht
Applied Cardiopulmonary Pathophysiology | Year: 2012

Death from heart disease has continued to diminish during the last two decades, but still half of those deaths are sudden, often occurring unexpectedly outside hospital, claiming at least 250.000 lives in Europe each year. What can we do to prevent this from happening and how can we successfully resuscitate the victim? When an arrhythmic sudden death occurs outside the hospital, the only chance for survival is recognition of the situation by a witness, the start of cardiac massage and a call to bring a defibrillator and experienced people to the scene as soon as possible. Increasing the number of people trained in resuscitation, and the density of the automatic external defibrillator in the community are important factors to increase the success rate of the resuscitation attempt. However, a real breakthrough requires the development of a device that recognizes cardiac arrest, sounds an alarm, and transmits the location of the victim, thereby shortening the time interval of the different steps in the chain of survival.


Winckers K.,Cardiovascular Research Institute Maastricht | Ten Cate H.,Cardiovascular Research Institute Maastricht | Hackeng T.M.,Cardiovascular Research Institute Maastricht
Blood Reviews | Year: 2013

Tissue factor pathway inhibitor (TFPI) is the main inhibitor of tissue factor (TF)-mediated coagulation. In atherosclerotic plaques TFPI co-localizes with TF, where it is believed to play an important role in attenuating TF activity. Findings in animal models such as TFPI knockout models and gene transfer models are consistent on the role of TFPI in arterial thrombosis as they reveal an active role for TFPI in attenuating arterial thrombus formation. In addition, ample experimental evidence exists indicating that TFPI has inhibitory effects on both smooth muscle cell migration and proliferation, both which are recognized as important pathological features in atherosclerosis development. Nonetheless, the clinical relevance of these antithrombotic and atheroprotective effects remains unclear. Paradoxically, the majority of clinical studies find increased instead of decreased TFPI antigen and activity levels in atherothrombotic disease, particularly in atherosclerosis and coronary artery disease (CAD). Increased TFPI levels in cardiovascular disease might result from complex interactions with established cardiovascular risk factors, such as hypercholesterolemia, diabetes and smoking. Moreover, it is postulated that increased TFPI levels reflect either the amount of endothelial perturbation and platelet activation, or a compensatory mechanism for the increased procoagulant state observed in cardiovascular disease. In all, the prognostic value of plasma TFPI in cardiovascular disease remains to be established. The current review focuses on TFPI in clinical studies of asymptomatic and symptomatic atherosclerosis, coronary artery disease and ischemic stroke, and discusses potential atheroprotective actions of TFPI. © 2013 Elsevier Ltd.

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