Cardiovascular Research Institute Maastricht CARIM

Maastricht, Netherlands

Cardiovascular Research Institute Maastricht CARIM

Maastricht, Netherlands

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Montero D.,University of Avignon | Montero D.,Universiteitssingel 50 | Montero D.,Cardiovascular Research Institute Maastricht CARIM | Vinet A.,University of Avignon | Roberts C.K.,University of California at Los Angeles
International Journal of Cardiology | Year: 2015

Background While aerobic exercise training may decrease arterial stiffness, the impact of combined aerobic and resistance training is unclear. Therefore, the aim of this study was to systematically review and quantify the effect of combined aerobic and resistance training on arterial stiffness, as determined by arterial pulse wave velocity (PWV), and compare it with aerobic training.Methods MEDLINE, EMBASE and Web of Science were searched through November 2013 for randomized controlled trials evaluating the effect of aerobic or combined aerobic and resistance training on PWV. A meta-analysis was performed to determine the standardized mean difference (SMD) in PWV between exercise and control groups. Subgroup analyses were used to study potential moderating factors.Results Twenty-one randomized controlled trials comparing exercise and control groups (overall n = 752), met the inclusion criteria. After data pooling, PWV was decreased in aerobic trained groups compared with controls (10 trials, SMD = - 0.52, 95% CI = - 0.76, - 0.27; P < 0.0001) but did not reach statistical significance in combined trained groups compared with controls (11 trials, SMD = - 0.23, 95% CI = - 0.50, 0.04; P = 0.10). The effect in aerobic trained groups did not differ compared with combined trained groups (P = 0.12). In addition, aerobic training resulted in significantly lower SMD in PWV compared with combined training in interventions including a higher volume of aerobic training or assessing carotid-femoral PWV.Conclusions These data suggest that combined aerobic and resistance training interventions may have reduced beneficial effects on arterial stiffness compared with control interventions, but do not appear to differ significantly with aerobic training alone. © 2014 Elsevier Ireland Ltd. All rights reserved.


Montero D.,Maastricht University | Montero D.,Cardiovascular Research Institute Maastricht CARIM
European Journal of Preventive Cardiology | Year: 2015

Background Maximal oxygen consumption (VO2max) is strongly associated with peripheral vasodilator function as determined by exercise-induced vasodilation. However, findings with regard to its relation with non-exercise-stimulated vasodilation are unclear. The purpose of this study was to systematically review published literature reporting associations between VO2max and endothelial function (EF) or smooth muscle function (SMF). Design and methods We conducted a systematic search of MEDLINE, Cochrane and Web of Science, since their inceptions until April 2014 for articles reporting the association between (a) VO2max during incremental exercise and (b) endothelium-dependent or -independent vasodilator function, by means of correlation and/or regression analysis. Results Fifty-six articles exploring 88 associations between VO2max and vascular EF or SMF were included, involving a total of 4159 healthy and diseased subjects. VO2max was determined by incremental cycle ergometer (64%), treadmill (33%) and cycle ergometer/treadmill (3%) exercise. Vasodilator function variables were assessed in the upper limb (86%), lower limb (10%) and both upper and lower limbs (3%). Most of the evaluated bivariate associations involved EF stimuli such as flow-mediated dilation (FMD) (n = 29) or blood flow occlusion (BFO) (n = 18). VO2max was significantly associated with FMD and BFO in 59% and 67% of bivariate associations and 46% and 33% of age-independent associations, respectively. Explored bivariate associations regarding SMF involved sodium nitroprusside (SNP) iontophoresis (n = 7) and nitrate-mediated dilation (NMD) (n = 4). VO2max was associated with NMD in 50% of bivariate associations and 50% of age-independent associations. VO2max was not associated with SNP iontophoresis. Results were similar for associations including only healthy subjects. Conclusions The association between VO2max and EF or SMF is moderately frequent and independent of health status, despite very few studies having assessed vasodilator function in the lower limb. © 2014 European Society of Cardiology.


Schalkwijk C.G.,Maastricht University | Schalkwijk C.G.,Cardiovascular Research Institute Maastricht CARIM
Diabetologia | Year: 2015

Over the years, new research has elucidated the importance of the very fast formation of AGEs by the highly reactive methylglyoxal (MGO). It has become clear that MGO triggers maladaptive responses in vascular tissue. To counteract the deleterious effects of MGO, organisms have an enzymatic glyoxalase defence system in which MGO is converted to d-lactate, with glyoxalase 1 (GLO1) as the key enzyme in this system. Significant progress has been made towards the understanding of the MGO–GLO1 pathway in the pathogenesis of vascular disease in diabetes. This commentary highlights some lines of current research and future perspectives. The work conducted so far is only the starting point—in the coming 50 years, the MGO–GLO1 pathway will be the subject of intensified research, with special focus on pathophysiological pathways, the use of this system for early screening and risk prediction, and the development of intervention strategies for preventing vascular complications in people with and without diabetes. This is one of a series of commentaries under the banner ‘50 years forward’, giving personal opinions on future perspectives in diabetes, to celebrate the 50th anniversary of Diabetologia (1965–2015). © 2015, The Author(s).


Klaassen E.M.M.,Maastricht University | Thonissen B.E.J.T.,Maastricht University | van Eys G.,Cardiovascular Research Institute Maastricht CARIM | Dompeling E.,Maastricht University | Jobsis Q.,Maastricht University
Allergy, Asthma and Clinical Immunology | Year: 2013

The aetiology of childhood asthma is complex. An early dysfunction in the immunological development of the innate immune system in combination with environmental factors possibly triggers asthma. CD14 and toll-like receptors are important components of the innate immune system. The aim of this systematic review was to obtain a better insight into the relation between CD14 and toll-like receptors and childhood asthma in Caucasians. We searched PubMed and EMBASE for relevant articles. In total, 44 articles were included. The quality of the selected studies was independently assessed by the first two authors using the Newcastle-Ottawa quality assessment scale. Toll-like receptor 2, toll-like receptor 6, toll-like receptor 9, and toll-like receptor 10 appear to have some association with childhood asthma in Caucasians. The evidence for a relation of CD14 with childhood asthma is limited. In conclusion, there is no convincing evidence yet for a role of CD14 and toll-like receptors in relation to childhood asthma. Future studies should include haplotype analysis and take environmental factors into account to further clarify the role of CD14 and toll-like receptors on childhood asthma. © 2013 Klaassen et al.; licensee BioMed Central Ltd.


De Saint-Hubert M.,Nuclear Medicine | De Saint-Hubert M.,Cardiovascular Research Institute Maastricht CARIM | Bauwens M.,Nuclear Medicine | Mottaghy F.M.,Nuclear Medicine | Mottaghy F.M.,RWTH Aachen
Current Pharmaceutical Design | Year: 2014

Evasion of apoptosis is one of the hallmarks of cancer and any effective therapy primarily attempts to induce apoptosis. The evaluation of the degree of success of cancer therapy is currently mainly based on clinical and laboratory parameters and in a later stage on tumor shrinkage. However, none of these parameters provide an objective and early analysis of a therapeutic effect. Molecular imaging may provide a tool for this purpose by using not only pathophysiological but also biochemical effects of the therapy. First in the field, FDG-PET has been explored and demonstrated to offer insight in the amount of viable cells, even though false positives are commonly due to the lack of specificity of this particular radiopharmaceutical. More specific markers target the dying cells instead of those remaining alive. Specific apoptosis markers have been developed of which the radiolabeled Annexin A5 is the most intensely studied probe. Site-specific labeling strategies have improved this imaging probe with good results both in pre-clinical studies and in clinical trials, with promises for clinical applications. Caspase sensitive probes, such as the isatines, can also effectively image apoptosis but are limited due to the high background activities. More recent discoveries of small apoptosis sensitive probes, such as 18F-ML10, are currently being explored. In this review, the most important apoptosis sensitive probes are described from both a pre-clinical and a clinical perspective, highlighting their potential but also their limitations as an early marker for therapeutic success. It seems that apoptosis imaging can help to guide therapy, not by replacing the current methodology but by providing additional and useful information. © 2014 Bentham Science Publishers.


Jetten N.,Cardiovascular Research Institute Maastricht CARIM | Verbruggen S.,Cardiovascular Research Institute Maastricht CARIM | Gijbels M.J.,Cardiovascular Research Institute Maastricht CARIM | Post M.J.,Cardiovascular Research Institute Maastricht CARIM | And 2 more authors.
Angiogenesis | Year: 2014

Objective: Macrophages show extreme heterogeneity and different subsets have been characterized by their activation route and their function. For instance, macrophage subsets are distinct by acting differently under pathophysiological conditions such as inflammation and cancer. Macrophages also contribute to angiogenesis, but the role of various specific subsets in angiogenesis has not been thoroughly investigated. Methods and results: Matrigel supplemented with macrophage subsets [induced by IFNγ (M1), IL-4 (M2a) or IL-10 (M2c)] was injected subcutaneously in C57BL/6 J mice and analyzed by CD31 staining after 14 days. Increased numbers of endothelial cells and tubular structures were observed in M2-enriched plugs compared to control and other subsets. Additionally, more tubular structures formed in vitro in the presence of M2 macrophages or their conditioned medium. To identify a mechanism for the pro-angiogenic effect, gene expression of angiogenic growth factors was analyzed. Induced expression of basic fibroblast growth factor (Fgf2), insulin-like growth factor-1 (Igf1), chemokine (C-C motif) ligand 2 (Ccl2) and placental growth factor (Pgf) was observed in M2 macrophages. Using a blocking antibody of PlGF to inhibit M2c induced angiogenesis resulted in mildly reduced (40 %) tube formation whereas neutralization of FGF-2 (M2a) signaling by sFGFR1-IIIc affected tube formation by nearly 75 %. Conclusions: These results indicate that macrophages polarized towards an M2 phenotype have a higher angiogenic potential compared to other subsets. Furthermore, we propose FGF signaling for M2a- and PlGF signaling for M2c-induced angiogenesis as possible working mechanisms, yet, further research should elucidate the exact mechanism for M2-induced angiogenesis. © 2013 Springer Science+Business Media Dordrecht.


Linz D.,Universitatsklinikum des Saarlandes | Schotten U.,Cardiovascular Research Institute Maastricht CARIM | Neuberger H.-R.,Universitatsklinikum des Saarlandes | Bohm M.,Universitatsklinikum des Saarlandes | Wirth K.,Sanofi S.A.
Heart Rhythm | Year: 2011

BACKGROUND Obstructive sleep apnea (OSA) causes negative tracheal pressure (NTP) and is associated with atrial fibrillation (AF). OBJECTIVE This study aimed to determine the mechanism of atrial electrophysiological changes during tracheal occlusion with or without applied NTP and to evaluate the role of vagal activation, Na +/H +exchanger (NHE), and ATP-dependent potassium channels (K ATP). METHODS Seventeen closed-chest pigs were anesthetized with urethane, and an endotracheal tube was placed to apply NTP (up to -100 mbar), comparable to clinically observed OSA in patients by a negative pressure device for a time period of 2 minutes. Right atrial refractory periods (AERP) and AF inducibility were measured transvenously by a monophasic action potential recording and stimulation catheter. RESULTS All tracheal occlusions with and without applied NTP resulted in comparable increases in blood pressure and hypoxemia. NTP shortened AERP (157.0 ± 2.8 to 102.1 ± 6.2 ms; P <.0001) and enhanced AF inducibility during AERP measurements from 0% at baseline to 90% (P <.00001) during NTP. Release of NTP resulted in a prompt restoration of sinus rhythm, and AERP returned to normal. NTP-induced AERP shortening and AF inducibility were prevented by atropine or vagotomy. Neither the NHE blocker cariporide nor the K ATP channel blocker glibenclamide abolished NTP-induced AERP shortening. By contrast, tracheal occlusion without applied NTP caused comparable changes in blood gases but did not induce AERP shortening or AF inducibility. CONCLUSION NTP during obstructive events is a strong trigger for AF compared with changes in blood gases alone. NTP caused AERP shortening and increased susceptibility to AF mainly by enhanced vagal activation. AERP shortening was not prevented by K ATP channel blockade or NHE blockade. © 2011 Heart Rhythm Society.


Linz D.,Universitatsklinikum des Saarlandes | Mahfoud F.,Universitatsklinikum des Saarlandes | Schotten U.,Cardiovascular Research Institute Maastricht CARIM | Ukena C.,Universitatsklinikum des Saarlandes | And 3 more authors.
Journal of Cardiovascular Electrophysiology | Year: 2013

Renal Denervation and Baroreflex Stimulation Introduction This study was designed to compare the effect of electrical baroreflex stimulation (BRS) at an intensity used in hypertensive patients and renal denervation (RDN) on atrial electrophysiology. BRS and RDN reduce blood pressure and global sympathetic drive in patients with resistant hypertension. Whereas RDN decreases sympathetic renal afferent nerve activity, leading to decreased central sympathetic drive, BRS modulates autonomic balance by activation of the baroreflex, resulting in both reduced sympathetic drive and increased vagal activation. Increased vagal tone potentially shortens atrial refractoriness resulting in a stabilization of reentry circuits perpetuating atrial fibrillation (AF). Methods and Results In normotensive anesthetized pigs (n = 12), we compared the acute effect of BRS and RDN on blood pressure, atrial effective refractory period (AERP), and inducibility of AF. Electrical BRS was titrated to result in comparable heart rate and blood pressure reduction compared to irreversible RDN. BRS resulted in a rapid and pronounced shortening of AERP (from 162 ± 8 milliseconds to 117 ± 16 milliseconds, P = 0.001) associated with increased AF-inducibility from 0% to 82%. This shortening in AERP was completely reversible after stopping BRS. After administration of atropine, AF-inducibility during BRS was attenuated. Ventricular repolarization was not modulated by BRS. In RDN, AF was not inducible; however, it did not prevent BRS-induced shortening of AERP. Conclusion RDN and BRS resulting in comparable blood pressure and heart rate reductions differently influence atrial electrophysiology. Vagally mediated shortening of AERP, resulting in increased AF-inducibility, was observed with BRS but not with RDN. © 2013 Wiley Periodicals, Inc.


Weber C.,RWTH Aachen | Weber C.,Cardiovascular Research Institute Maastricht CARIM
Thrombosis and Haemostasis | Year: 2010

The difficulties in cardiovascular drug development have been exposed by recent clinical trials, which have uncovered various limitations of promising drug candidates. Yet, the imperative to improve medical treatment of atherosclerosis in aging populations afflicted by metabolic disease remains unbroken. Herein alternatives to metabolically active compounds such as glitazones and torcetrapib are introduced and discussed, namely CC chemokine receptor 5 (CCR5) antagonists recently approved for treatment of patients with human immunodeficiency virus-1, interceptors of proatherogenic chemokine interactions, and actively protective pathways. A combination of different strategies may yield improved safety profiles of these therapeutics. © Schattauer 2010.


Sabrkhany S.,Cardiovascular Research Institute Maastricht CARIM | Sabrkhany S.,VU University Amsterdam | Griffioen A.W.,VU University Amsterdam | oude Egbrink M.G.A.,Cardiovascular Research Institute Maastricht CARIM
Biochimica et Biophysica Acta - Reviews on Cancer | Year: 2011

Coagulation abnormalities occur frequently in cancer patients. It is becoming evident that blood platelets have an important function in this process. However, understanding of the underlying mechanisms is still very modest. In this review, we discuss the role of platelets in tumor angiogenesis and growth and suggest their potential significance in malignancies. Platelets contain various pro-and antiangiogenic molecules, which seem to be endocytosed and sequestered in different populations of α-granules. Furthermore, tumor endothelial cells are phenotypically and functionally different from endothelial cells in healthy tissue, stimulating local platelet adhesion and subsequent activation. As a consequence, platelets are able to secrete their angiogenic and angiostatic content, most likely in a regulated manner. The overall effect of these platelet-endothelium interactions appears to be proangiogenic, stimulating tumor angiogenesis. We favor the view that local adhesion and activation of blood platelets and dysregulation of coagulation represent underestimated pathways in the progression of cancer. © 2010 Elsevier B.V.

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