Papers by Veronique Roelants
Cardiovascular Research, Oct 8, 2013
Mesenchymal stem cells (MSCs) are widely used for cell therapy, particularly for the treatment of... more Mesenchymal stem cells (MSCs) are widely used for cell therapy, particularly for the treatment of ischaemic heart disease. Mechanisms underlying control of their metabolism and proliferation capacity, critical elements for their survival and differentiation, have not been fully characterized. AMP-activated protein kinase (AMPK) is a key regulator known to metabolically protect cardiomyocytes against ischaemic injuries and, more generally, to inhibit cell proliferation. We hypothesized that AMPK plays a role in control of MSC metabolism and proliferation. MSCs isolated from murine bone marrow exclusively expressed the AMPKa1 catalytic subunit. In contrast to cardiomyocytes, a chronic exposure of MSCs to hypoxia failed to induce cell death despite the absence of AMPK activation. This hypoxic tolerance was the consequence of a preference of MSC towards glycolytic metabolism independently of oxygen availability and AMPK signalling. On the other hand, A-769662, a well-characterized AMPK activator, was able to induce a robust and sustained AMPK activation. We showed that A-769662-induced AMPK activation inhibited MSC proliferation. Proliferation was not arrested in MSCs derived from AMPKa1-knockout mice, providing genetic evidence that AMPK is essential for this process. Among AMPK downstream targets proposed to regulate cell proliferation, we showed that neither the p70 ribosomal S6 protein kinase/eukaryotic elongation factor 2-dependent protein synthesis pathway nor p21 was involved, whereas p27 expression was increased by A-769662. Silencing p27 expression partially prevented the A-769662-dependent inhibition of MSC proliferation. MSCs resist hypoxia independently of AMPK whereas chronic AMPK activation inhibits MSC proliferation, p27 being involved in this regulation.
Journal of Nuclear Cardiology, Dec 18, 2014
Frontiers in Cardiovascular Medicine
BackgroundNon-invasive evaluation of left atrial structural and functional remodeling should be c... more BackgroundNon-invasive evaluation of left atrial structural and functional remodeling should be considered in all patients with persistent atrial fibrillation (AF) to optimal management. Speckle tracking echocardiography (STE) has been shown to predict AF recurrence after catheter ablation; however in most studies, patients had paroxysmal AF, and STE was performed while patients were in sinus rhythm.AimThe aim of this study was to evaluate the ability of STE parameters acquired during persistent AF to assess atrial fibrosis measured by low voltage area, and to predict maintenance of sinus rhythm of catheter ablation.MethodsA total of 94 patients (69 men, 65 ± 9 years) with persistent AF prospectively underwent measurement of Global Peak Atrial Longitudinal Strain (GPALS), indexed LA Volume (LAVI), E/e′ ratio, and LA stiffness index (the ratio of E/e′ to GPALS) by STE prior to catheter ablation, while in AF. Low-voltage area (LVA) was assessed by electro-anatomical mapping and catego...
Integrin-Targeted MicroSPECT-CT Imaging of Inflamed Atherosclerotic Plaques in Mice
Circulation, 2012
Background and aim. αVβ3 integrin is expressed in endothelial cells and macrophages of atheroscle... more Background and aim. αVβ3 integrin is expressed in endothelial cells and macrophages of atherosclerotic plaques and may represent a valuable marker of plaque vulnerability. To test this, we evaluated whether the integrin specific tracer 99mTc-NC100692 can be used for imaging inflamed atherosclerotic lesions in mice. Methods. Hyperlipidemic ApoE-/- mice on a Western diet (n=7) and normally fed adult C57BL6 control mice (n=4) were injected with NC100692 (51.8 ± 3.7 MBq). A blocking peptide was infused immediately before the tracer injection in 3 additional ApoE-/- mice that served as control. After 90 min, the animals were imaged with a µSPECT system, and immediately thereafter on a MDCT system to obtain contrast-enhanced images of the aorta. Images from both modalities were fused and the signal was quantified in the aortic arch and in the vena cava for blood pool activity substraction. The aorta was carefully dissected after imaging for gamma well counting and histology. Results. A significantly higher tracer uptake (defined as the counts/pixel ratio between the aortic arch and the vena cava) was observed between the ApoE-/- mice and 2 control mice groups (1.56 ± 0.33 vs 0.82 ± 0.24 (C57BL6) vs 0.98 ± 0.11 (blocking peptide) respectively; p<0.05, see graph). Furthermore, a significant tracer activity was observed by gamma counting in the aorta of ApoE-/- mice compared with 2 control mice groups (0.015 ± 0.004 vs 0.007 ± 0.006 µCi/mg of tissue; p<0.05). Finally, immunostaining with antibodies against integrin correlated well with the presence of macrophages into atherosclerotic lesions of ApoE-/- mice. Conclusion. NC100692 allows for the in vivo detection of inflamed atherosclerotic plaques in mice and may thus represent an interesting non invasive approach for identifying vulnerable plaques in patients
Evaluation of the novel high-resolution rodent linoview SPECT for myocardial perfusion Imaging of mice
European Journal of Nuclear Medicine and Molecular Imaging, 2007
Prognostic value of DMSA scintigraphy in children with acute pyelonephritis: First results from a prospective study
European Journal of Nuclear Medicine and Molecular Imaging, 2001
Value of combined simple clinical assessment and planar lung perfusion scan for the diagnosis of pulmonary embolism (PE)
European Journal of Nuclear Medicine and Molecular Imaging, 1999
Archives of Cardiovascular Diseases Supplements, 2019
This mouse model recapitulates all the clinical features of DCM as well as the metabolic features... more This mouse model recapitulates all the clinical features of DCM as well as the metabolic features, such as cardiac glucose overload, progressing into chronic heart failure and middle-aged death. Aim Using our DCM mouse model, we will test whether reducing cardiac glucose overload to the heart diminishes or exacerbates cardiac and metabolic dysfunction. To his end, we will ablate the primary glucose transporter GLUT 4 either partially or completely in DCM mice to diminish glucose uptake to the heart. Results We generated cardiac specific deletions of YME1L and GLUT4 by crossing the cardiomyocyte specific Crerecombinase drive Myh6-Cre to conditional YME1LLoxp/LoxP and SLC2A4Loxp/LoxP mice. Cardiac function will be assessed using echocardiography and mitochondrial activity using high resolution oxygraphy (Oroboros) in isolated cardiac mitochondria. Conclusion and perspectives Our studies will allow us to determine the importance of glucose uptake and usage in the failing adult heart.
Circulation. Cardiovascular imaging, 2017
We appreciate the interest in our article from Drs Chung and Kim, who raise the important issue o... more We appreciate the interest in our article from Drs Chung and Kim, who raise the important issue over the leading cause of plaque destabilization and its potential dramatic consequences. They rightly point out that plaque inflammation, major criteria of plaque vulnerability, is a systemic process while plaque neovascularization is a purely local process. They also noticed that neovascularization is a crucial source of intraplaque hemorrhage, which is associated with plaque progression and rupture. We completely agree with that. In our study, we demonstrated that inflammation was not systematically associated with the degree of neovascularization within the plaque, suggesting a temporal separation of these processes. We could find no correlation between either of these 2 major determinants of plaque vulnerability, highlighting the practical challenges in defining imaging strategies with which to assess plaque vulnerability and future risk of clinical events. We disagree with Drs Chung and Kim when they said that previous reports demonstrated the association between IPN and future stroke events. Staub et al 2 demonstrated an association of IPN with past clinical events but not with future events. That is the crucial point. Kim et al 3 failed also to demonstrate an association between IPN and 1-year cardiovascular events. More evidence exists between inflammation and subsequent cardiovascular events. Therefore, we hypothesize that inflammation is probably the more useful parameter (than the presence of neovascularization) in discriminating patients at a high versus low risk for presenting acute syndromes. Which plaque feature is the best predictor of a clinical event? The question is still open. We agree with Drs Chung and Kim that this is an important area for future investigations.
Transplantation, Aug 1, 2017
With the exception of liver transplantation, there is no cure for hemophilia, which is currently ... more With the exception of liver transplantation, there is no cure for hemophilia, which is currently managed by preemptive replacement therapy. Liver-derived stem cells are in clinical development for inborn and acquired liver diseases and could represent a curative treatment for hemophilia A. The liver is a major factor VIII (FVIII) synthesis site, and mesenchymal stem cells have been shown to control joint bleeding in animal models of hemophilia. Adult-derived human liver stem cells (ADHLSCs) have mesenchymal characteristics and have been shown able to engraft in and repopulate both animal and human livers. Thus, the objectives were to evaluate the potency of ADHLSCs to control bleeding in a hemophilia A patient and assess the biodistribution of the cells after intravenous injection. A patient suffering from hemophilia A was injected with repeated doses of ADHLSCs via a peripheral vein (35 million In-oxine-labeled cells, followed by 125 million cells the next day, and 3 infusions of 2...
Tracking Cancer-Targeted MSC with PET Imaging
Shah/Stem Cell Therapeutics for Cancer, 2013
Journal of Nuclear Cardiology, 2014
European Heart Journal - Cardiovascular Imaging, 2012
Repaired tetralogy of Fallot (rtoF) patients are at risk of atrial or ventricular tachyarrhythmia... more Repaired tetralogy of Fallot (rtoF) patients are at risk of atrial or ventricular tachyarrhythmia and sudden cardiac death. We investigated the significance of right atrial (RA) and right ventricular (RV) anatomy and function for arrhythmia prediction by cardiac magnetic resonance imaging (CMR). Methods: One-hundred-and-fifty-four rtoF adults who underwent CMR were studied with the pre-specified endpoint of new-onset atrial or ventricular arrhythmia (sustained ventricular tachycardia/ventricular fibrillation) during a longitudinal follow-up. Results: Median age was 31 (IQR:22-40), median follow-up was 5.6 (IQR:4.6-7.0) years Atrial tachyarrhythmia (n=11) was predicted by maximal right atrial area indexed to body surface area (RAAi) on cine-CMR (Hazard ratio; HR1.17, 95%CI 1.07-1.28 per cm2/m2; P=0.0005, survival ROC curve analysis, area under curve; AUC 0.74[0.66-0.81]; cut-off value 16cm2/m2). Atrial arrhythmia-free survival was reduced in patients with RAAi ≥16cm2/m2 (Logrank; P=0.0001). RV restrictive physiology on echocardiography (n=38) related to higher RAAi (P=0.02) but did not predict atrial tachyarrhythmia (P=0.057). RV restrictive physiology patients had similar RV dilatation and exercise impairment to remaining patients representing a different phenotype from previous reports. Ventricular arrhythmia (n=9) was predicted by CMR RV outflow tract (RVOT) akinetic area length (HR1.05,95%CI 1.01-1.09 per mm; P=0.003, survival ROC analysis, AUC 0.77[0.83-0.61];cut-off value 30mm) and decreased RV ejection fraction (HR0.93 95%CI 0.87-0.99 per %; P=0.03, respectively). Ventricular arrhythmia-free survival was reduced in patients with RVOT akinetic region length .30mm (Logrank; P=0.02). Conclusions: RAAi predicts atrial arrhythmia and RVOT akinetic region length predicts ventricular arrhythmia in late follow-up of rtoF. These are simple, feasible measurements for serial surveillance and risk stratification of rtoF patients.
Nuclear Medicine Communications, 2006
Objective We determined the value of attenuation correction (AC) of myocardial perfusion estimati... more Objective We determined the value of attenuation correction (AC) of myocardial perfusion estimation with 99m Tc-MIBI SPECT in overweight patients by comparison of uncorrected (filtered back-projection (FBP) and corrected (an iterative algorithm with a measured attenuation coefficients map (FL-AC)) 99m Tc-MIBI relative uptake to perfusion data obtained in the same patients with NH 3 PET. In addition, the impact of attenuation correction for the assessment of myocardial viability with 99m Tc-MIBI SPECT was determined using FDG PET as the reference method. Methods Thirty consecutive overweight patients (BMI = 28 ± 4) with left ventricular dysfunction underwent a resting 99m Tc-MIBI SPECT and a PET study (NH 3 and FDG). 99m Tc-MIBI SPECT scans were reconstructed without attenuation correction (FBP) and with attenuation correction (FL-AC). The left ventricle was divided into 16 segments, in which the relative uptake was quantified using circumferential profiles. A relative uptake Z 60% was considered consistent with viable myocardium for FDG and MIBI. The absolute difference between 99m Tc-MIBI SPECT and NH 3 PET uptakes was less pronounced in the inferior (12 ± 10% vs. 17 ± 12%, P < 0.001), anteroseptal (12 ± 11% vs. 16 ± 12%, P = 0.009) and septal (15 ± 12% vs. 18 ± 14%, P = 0.003) regions (FL-AC vs. FBP, respectively). The sensitivity of MIBI for diagnosing myocardial viability increased from 83 to 100% (P = 0.034), without loss in specificity. Tc-MIBI SPECT in the inferior, anteroseptal and septal regions and increases its sensitivity for the diagnosis of myocardial viability. Nucl Med Commun 27:815-821 c 2006 Lippincott Williams & Wilkins.
Gut, 2012
Objective-Growing evidence suggests that a phenotypic switch converting pancreatic acinar cells t... more Objective-Growing evidence suggests that a phenotypic switch converting pancreatic acinar cells to duct-like cells can lead to pancreatic intraepithelial neoplasia (PanIN) and eventually to invasive pancreatic ductal adenocarcinoma. Histologically, the onset of this switch is characterised by the co-expression of acinar and ductal markers in acini, a lesion called acinar-to-ductal metaplasia (ADM). Transcriptional regulators required to initiate ADM still remain unknown, yet need to be identified to characterise the regulatory networks that drive ADM. Here we investigate the role of the ductal transcription factors Hepatocyte Nuclear Factor 6 (HNF6, also known as Onecut1)and SRY-related HMG box factor 9 (Sox9) in ADM.
The predictive value of serum thyroglobulin in the follow-up of differentiated thyroid cancer
European Journal of Nuclear Medicine, 1997
A strict and careful strategy has to be adopted to cure thyroid cancer. Diagnostic iodine-131 who... more A strict and careful strategy has to be adopted to cure thyroid cancer. Diagnostic iodine-131 whole-body scan (WBS) and serum thyroglobulin (Tg) are important tools to detect thyroid remnants after thyroidectomy and radioiodine therapy. The aim of this retrospective study was to compare the relative sensitivity of WBS and Tg in the detection of thyroid remnants or metastases and to evaluate the predictive value of Tg in the clinical and scintigraphic course of the disease. Ninety-three patients were followed up after total thyroidectomy and the administration 4-6 weeks later of an ablative dose of 100 or 150 mCi 131I. Eighty-five percent of the patients were free of regional or distant metastases. The follow-up scheme included clinical examination of the patient followed by WBS, Tg, thyroid-stimulating hormone and free thyroxine measurements performed 4 weeks after thyroxine withdrawal and the observance of a low-iodine diet for at least 1 week. WBS (+) patients received a 100- or 150-mCi therapeutic dose of 131I. All patients were further followed up in the same way every 6 months until both WBS and Tg became negative, and thereafter at 1-, 2- and 4-year intervals. Six months after the postoperative radioiodine treatment (first visit), the sensitivity of WBS and Tg was 87% and 26% respectively. Among patients who were WBS(+) at the first visit, 95% of those who were Tg(-) and 47% of those who were Tg(+) had become disease-free at a median of 4 years after surgery (chi2=13.6; P&lt;0.05). Patients whose tests were both positive required more radioiodine to be cured (335+/-90 vs 250+/-95 mCi; P&lt;0.05). Our data indicate that in early diagnosed thyroid cancer, serum Tg measured 6 months after the postoperative 131I ablative dose is less sensitive than WBS for the demonstration of persistence of residual thyroid tissue but provides predictive information on the disease course. WBS(+) and Tg(-) patients are cured earlier and with less radioiodine than those who remain Tg(+).
Exercise gated planar myocardial perfusion imaging using technetium-99m sestamibi for the diagnosis of coronary artery disease: an alternative to exercise tomographic imaging
European Journal of Nuclear Medicine, 1995
Single-photon emission tomography (SPET) using technetium-99m labelled myocardial tracers (e.g. 9... more Single-photon emission tomography (SPET) using technetium-99m labelled myocardial tracers (e.g. 99mTc-sestamibi) has become one of the most popular myocardial imaging methods for the diagnosis of coronary artery disease (CAD). This prospective study was designed to evaluate the diagnostic performance of 99mTc-sestamibi exercise gated planar myocardial imaging by comparison with both visual and quantitative analyses of SPET. The study was conducted in 115 consecutive patients with known or suspected CAD, including 54 patients with a previous myocardial infarction (MI), referred for exercise testing prior to coronary angiography. Multi-gated planar imaging and SPET were performed after bicycle exercise. The end-diastolic (ED) and SPET images were visually scored (SVi). Myocardial uptake was quantitated on SPET slices using maximum count circumferential profiles (SQu) and defect extent was measured by comparison with gender-matched data sets obtained from 27 controls (&lt; 5% likelihood of CAD). CAD was defined as coronary artery stenosis &gt; 50% and/or regional wall motion abnormality. The cut-off criteria for positivity of the three procedures were determined from receiver operating characteristic (ROC) curves derived from the data of patients without previous MI. The area under the ROC curves was similar for ED, SVi and SQu. This was confirmed by the analysis of sensitivity performed using the ROC curve-derived cut-off criteria, in patients with or without previous MI. SVi was more sensitive than ED in identifying the diseased vessel(s) (ED: 41% vs SVi: 80%; P &lt; 0.0005) but ED was more specific in this respect (ED: 79% vs SVi: 61%; P &lt; 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)
Endocrinology, Diabetes & Metabolism Case Reports, 2019
Summary A 26-year-old woman presented with persistent headache and tiredness. Biological investig... more Summary A 26-year-old woman presented with persistent headache and tiredness. Biological investigations disclosed a moderate inflammatory syndrome, low PTH-hypercalcemia and complete anterior hypopituitarism. A magnetic resonance imaging (MRI) of the pituitary gland was performed and revealed a symmetric enlargement with a heterogeneous signal. Ophthalmological examination showed an asymptomatic bilateral anterior and posterior uveitis, and a diagnosis of pituitary sarcoidosis was suspected. As the localization of lymphadenopathies on the fused whole-body FDG-PET/computerized tomography (CT) was not evoking a sarcoidosis in first instance, an excisional biopsy of a left supraclavicular adenopathy was performed showing classic nodular sclerosis Hodgkin’s lymphoma (HL). A diagnostic transsphenoidal biopsy of the pituitary gland was proposed for accurate staging of the HL and surprisingly revealed typical granulomatous inflammation secondary to sarcoidosis, leading to the diagnosis of ...
Impact of COVID-19 Pandemic on Cardiovascular Testing in Asia
JACC: Asia, 2021
JACC: Cardiovascular Imaging, 2021
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in Engli... more Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre -including this research content -immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
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Papers by Veronique Roelants