Author
Sofie Bekaert
Other affiliations: Ghent University Hospital
Bio: Sofie Bekaert is an academic researcher from Ghent University. The author has contributed to research in topics: Population & Telomere. The author has an hindex of 29, co-authored 77 publications receiving 3300 citations. Previous affiliations of Sofie Bekaert include Ghent University Hospital.
Topics: Population, Telomere, Biobank, Telomerase, Pulse wave velocity
Papers published on a yearly basis
Papers
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University of Bristol1, Medical Research Council2, Newcastle University3, University of London4, University of Glasgow5, University of Southampton6, Seconda Università degli Studi di Napoli7, Ghent University8, University of Southern Denmark9, University of British Columbia10, Tulane University11, University of Edinburgh12, University of Michigan13, University of Washington14, University of Utah15, Kyungpook National University16, Yeshiva University17, Rutgers University18, Kyushu University19, King's College London20, Katholieke Universiteit Leuven21, Lund University22, Umeå University23, University of Calgary24, The Chinese University of Hong Kong25, University of Groningen26, University of Texas Southwestern Medical Center27, National Institutes of Health28
TL;DR: Telomere length is longer in females than males, although this difference was not universally found in studies that did not use Southern blot methods, and further research on explanations for the methodological differences is required.
370 citations
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TL;DR: It is shown that TL of peripheral blood leukocytes primarily reflects the burden of increased oxidative stress and inflammation, whether or not determined by an increasingly unhealthy lifestyle, while the association with classical CVD risk factors is limited.
Abstract: Evidence assembled over the last decade shows that average telomere length (TL) acts as a biomarker for biological aging and cardiovascular disease (CVD) in particular. Although essential for a more profound understanding of the underlying mechanisms, little reference information is available on TL. We therefore sought to provide baseline TL information and assess the association of prevalent CVD risk factors with TL in subjects free of overt CVD within a small age range. We measured mean telomere restriction fragment length of peripheral blood leukocytes in a large, representative Asklepios study cohort of 2509 community-dwelling, Caucasian female and male volunteers aged approximately 35-55 years and free of overt CVD. We found a manifest age-dependent telomere attrition, at a significantly faster rate in men as compared to women. No significant associations were established with classical CVD risk factors such as cholesterol status and blood pressure, yet shorter TL was associated with increased levels of several inflammation and oxidative stress markers. Importantly, shorter telomere length was associated with an increasingly unhealthy lifestyle, particularly in men. All findings were age and gender adjusted where appropriate. With these cross-sectional results we show that TL of peripheral blood leukocytes primarily reflects the burden of increased oxidative stress and inflammation, whether or not determined by an increasingly unhealthy lifestyle, while the association with classical CVD risk factors is limited. This further clarifies the added value of TL as a biomarker for biological aging and might improve our understanding of how TL is associated with CVD.
324 citations
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TL;DR: The binning algorithm resulted in an improved classification of hypertensive status compared with that of standard binning and facilitated the identification of relevant metabolites, and the involvement of alpha-1 acid glycoproteins and choline biochemistry in hypertension is suggested.
Abstract: As with every -omics technology, metabolomics requires new methodologies for data processing. Due to the large spectral size, a standard approach in NMR-based metabolomics implies the division of spectra into equally sized bins, thereby simplifying subsequent data analysis. Yet, disadvantages are the loss of information and the occurrence of artifacts caused by peak shifts. Here, a new binning algorithm, Adaptive Intelligent Binning (AI-Binning), which largely circumvents these problems, is presented. AI-Binning recursively identifies bin edges in existing bins, requires only minimal user input, and avoids the use of arbitrary parameters or reference spectra. The performance of AI-Binning is demonstrated using serum spectra from 40 hypertensive and 40 matched normotensive subjects from the Asklepios study. Hypertension is a major cardiovascular risk factor characterized by a complex biochemistry and, in most cases, an unknown origin. The binning algorithm resulted in an improved classification of hyperten...
219 citations
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TL;DR: PubMeth is a cancer methylation database that includes genes that are reported to be methylated in various cancer types that is based on text-mining of Medline/PubMed abstracts, combined with manual reading and annotation of preselected abstracts.
Abstract: Epigenetics, and more specifically DNA methylation is a fast evolving research area. In almost every cancer type, each month new publications confirm the differentiated regulation of specific genes due to methylation and mention the discovery of novel methylation markers. Therefore, it would be extremely useful to have an annotated, reviewed, sorted and summarized overview of all available data. PubMeth is a cancer methylation database that includes genes that are reported to be methylated in various cancer types. A query can be based either on genes (to check in which cancer types the genes are reported as being methylated) or on cancer types (which genes are reported to be methylated in the cancer (sub) types of interest). The database is freely accessible at http://www.pubmeth.org. PubMeth is based on text-mining of Medline/PubMed abstracts, combined with manual reading and annotation of preselected abstracts. The text-mining approach results in increased speed and selectivity (as for instance many different aliases of a gene are searched at once), while the manual screening significantly raises the specificity and quality of the database. The summarized overview of the results is very useful in case more genes or cancer types are searched at the same time.
181 citations
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TL;DR: It is concluded that, in healthy middle-aged subjects, the central-to-radial amplification of the pressure pulse is substantial, higher in men than in women, decreases with age, and is primarily associated with the carotid augmentation index.
Abstract: Central-to-peripheral amplification of the pressure pulse leads to discrepancies between central and brachial blood pressures. This amplification depends on an individual's hemodynamic and (patho)physiological characteristics. The aim of this study was to assess the magnitude and correlates of central-to-peripheral amplification in the upper limb in a healthy, middle-aged population (the Asklepios Study). Carotid, brachial, and radial pressure waveforms were acquired noninvasively using applanation tonometry in 1873 subjects (895 women) aged 35 to 55 years. Carotid, brachial, and radial pulse pressures were calculated, as well as the absolute and relative (with carotid pulse pressure as reference) amplifications. With subjects classified per semidecade of age, carotid-to-radial amplification varied from approximately 25% in the youngest men to 8% in the oldest women. Amplification was higher in men (20+/-14%) than in women (13+/-12%; P<0.001) and decreased with age (P<0.001) in both. Amplification over the brachial-to-radial path contributed substantially to the total amplification. In univariate analysis, the strongest correlation was found with the carotid augmentation index (-0.51 in women; -0.47 in men; both P<0.001). In a multiple linear regression model with carotid-to-radial amplification as the dependent variable, carotid augmentation index, total arterial compliance, and heart rate were identified as the 3 major determinants of upper limb pressure amplification (R2=0.36). We conclude that, in healthy middle-aged subjects, the central-to-radial amplification of the pressure pulse is substantial. Amplification is higher in men than in women, decreases with age, and is primarily associated with the carotid augmentation index.
176 citations
Cited by
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University of Chicago1, University of Padua2, McGill University3, Johns Hopkins University4, French Institute of Health and Medical Research5, Uppsala University6, University of California, San Francisco7, MedStar Washington Hospital Center8, Katholieke Universiteit Leuven9, University of Liège10, Harvard University11, Ghent University Hospital12, University of Toronto13
TL;DR: This document provides updated normal values for all four cardiac chambers, including three-dimensional echocardiography and myocardial deformation, when possible, on the basis of considerably larger numbers of normal subjects, compiled from multiple databases.
Abstract: The rapid technological developments of the past decade and the changes in echocardiographic practice brought about by these developments have resulted in the need for updated recommendations to the previously published guidelines for cardiac chamber quantification, which was the goal of the joint writing group assembled by the American Society of Echocardiography and the European Association of Cardiovascular Imaging. This document provides updated normal values for all four cardiac chambers, including three-dimensional echocardiography and myocardial deformation, when possible, on the basis of considerably larger numbers of normal subjects, compiled from multiple databases. In addition, this document attempts to eliminate several minor discrepancies that existed between previously published guidelines.
11,568 citations
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TL;DR: Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography and the European Association of Cardiovascular Imaging are presented.
Abstract: Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography : An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging
4,020 citations
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TL;DR: The primary goal of this update is to simplify the approach and thus increase the utility of the guidelines in daily clinical practice.
Abstract: Echocardiographic assessment of left ventricular (LV) diastolic function is an integral part of the routine evaluation of patients presenting with symptoms of dyspnea or heart failure. The 2009 American Society of Echocardiography (ASE) and European Association of Echocardiography (now European Association of Cardiovascular Imaging [EACVI]) guidelines for diastolic function assessment were comprehensive, including several two-dimensional (2D) and Doppler parameters to grade diastolic dysfunction and to estimate LV filling pressures.1 Notwithstanding, the inclusion of many parameters in the guidelines was perceived to render diastolic function assessment too complex, because several readers have interpreted the guidelines as mandating all the listed parameters in the document to fall within specified values before assigning a specific grade. The primary goal of this update is to simplify the approach and thus increase the utility of the guidelines in daily clinical practice.
LV diastolic dysfunction is usually the result of impaired LV relaxation with or without …
2,541 citations
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TL;DR: Coppe et al. as mentioned in this paper showed that human cells induced to senesce by genotoxic stress secrete myriad factors associated with inflammation and malignancy, including interleukin (IL)-6 and IL-8.
Abstract: PLoS BIOLOGY Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor Jean-Philippe Coppe 1 , Christopher K. Patil 1[ , Francis Rodier 1,2[ , Yu Sun 3 , Denise P. Mun oz 1,2 , Joshua Goldstein 1¤ , Peter S. Nelson 3 , Pierre-Yves Desprez 1,4 , Judith Campisi 1,2* 1 Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America, 2 Buck Institute for Age Research, Novato, California, United States of America, 3 Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America, 4 California Pacific Medical Center Research Institute, San Francisco, California, United States of America Cellular senescence suppresses cancer by arresting cell proliferation, essentially permanently, in response to oncogenic stimuli, including genotoxic stress. We modified the use of antibody arrays to provide a quantitative assessment of factors secreted by senescent cells. We show that human cells induced to senesce by genotoxic stress secrete myriad factors associated with inflammation and malignancy. This senescence-associated secretory phenotype (SASP) developed slowly over several days and only after DNA damage of sufficient magnitude to induce senescence. Remarkably similar SASPs developed in normal fibroblasts, normal epithelial cells, and epithelial tumor cells after genotoxic stress in culture, and in epithelial tumor cells in vivo after treatment of prostate cancer patients with DNA- damaging chemotherapy. In cultured premalignant epithelial cells, SASPs induced an epithelial–mesenchyme transition and invasiveness, hallmarks of malignancy, by a paracrine mechanism that depended largely on the SASP factors interleukin (IL)-6 and IL-8. Strikingly, two manipulations markedly amplified, and accelerated development of, the SASPs: oncogenic RAS expression, which causes genotoxic stress and senescence in normal cells, and functional loss of the p53 tumor suppressor protein. Both loss of p53 and gain of oncogenic RAS also exacerbated the promalignant paracrine activities of the SASPs. Our findings define a central feature of genotoxic stress-induced senescence. Moreover, they suggest a cell-nonautonomous mechanism by which p53 can restrain, and oncogenic RAS can promote, the development of age-related cancer by altering the tissue microenvironment. Citation: Coppe JP, Patil CK, Rodier F, Sun Y, Mun oz DP, et al. (2008) Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 6(12): e301. doi:10.1371/journal.pbio.0060301 Introduction Cancer is a multistep disease in which cells acquire increasingly malignant phenotypes. These phenotypes are acquired in part by somatic mutations, which derange normal controls over cell proliferation (growth), survival, invasion, and other processes important for malignant tumorigenesis [1]. In addition, there is increasing evidence that the tissue microenvironment is an important determinant of whether and how malignancies develop [2,3]. Normal tissue environ- ments tend to suppress malignant phenotypes, whereas abnormal tissue environments such at those caused by inflammation can promote cancer progression. Cancer development is restrained by a variety of tumor suppressor genes. Some of these genes permanently arrest the growth of cells at risk for neoplastic transformation, a process termed cellular senescence [4–6]. Two tumor suppressor pathways, controlled by the p53 and p16INK4a/pRB proteins, regulate senescence responses. Both pathways integrate multiple aspects of cellular physiology and direct cell fate towards survival, death, proliferation, or growth arrest, depending on the context [7,8]. Several lines of evidence indicate that cellular senescence is a potent tumor-suppressive mechanism [4,9,10]. Many poten- tially oncogenic stimuli (e.g., dysfunctional telomeres, DNA PLoS Biology | www.plosbiology.org damage, and certain oncogenes) induce senescence [6,11]. Moreover, mutations that dampen the p53 or p16INK4a/pRB pathways confer resistance to senescence and greatly increase cancer risk [12,13]. Most cancers harbor mutations in one or both of these pathways [14,15]. Lastly, in mice and humans, a senescence response to strong mitogenic signals, such as those delivered by certain oncogenes, prevents premalignant lesions from progressing to malignant cancers [16–19]. Academic Editor: Julian Downward, Cancer Research UK, United Kingdom Received June 27, 2008; Accepted October 22, 2008; Published December 2, 2008 Copyright: O 2008 Coppe et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abbreviations: CM, conditioned medium; DDR, DNA damage response; ELISA, enzyme-linked immunosorbent assay; EMT, epithelial–mesenchymal transition; GSE, genetic suppressor element; IL, interleukin; MIT, mitoxantrone; PRE, presenescent; PrEC, normal human prostate epithelial cell; REP, replicative exhaustion; SASP, senescence-associated secretory phenotype; SEN, senescent; shRNA, short hairpin RNA; XRA, X-irradiation * To whom correspondence should be addressed. E-mail: jcampisi@lbl.gov [ These authors contributed equally to this work. ¤ Current address: Genomics Institute of the Novartis Research Foundation, San Diego, California, United States of America December 2008 | Volume 6 | Issue 12 | e301
2,150 citations
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TL;DR: There is such a diversity of DNA methylation profiling techniques that it can be challenging to select one, and this Review discusses the different approaches and their relative merits and introduces considerations for data analysis.
Abstract: Methylation of cytosine bases in DNA provides a layer of epigenetic control in many eukaryotes that has important implications for normal biology and disease. Therefore, profiling DNA methylation across the genome is vital to understanding the influence of epigenetics. There has been a revolution in DNA methylation analysis technology over the past decade: analyses that previously were restricted to specific loci can now be performed on a genome-scale and entire methylomes can be characterized at single-base-pair resolution. However, there is such a diversity of DNA methylation profiling techniques that it can be challenging to select one. This Review discusses the different approaches and their relative merits and introduces considerations for data analysis.
1,521 citations