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622 results on '"Mokry, M"'

2. Human atherosclerotic plaque macrophages associate with clinical presentation and follow diverse lineage differentiation routes

Author

Prange, K, primary, Bel-Bordes, G, additional, Depuydt, M A C, additional, Kempkes, R W M, additional, De Jong, M D M, additional, Mol, B M, additional, Slutter, B, additional, Bot, I, additional, Neele, A E, additional, De Kleijn, D P V, additional, De Borst, G J, additional, Kuiper, J, additional, Pasterkamp, G, additional, Mokry, M, additional, and De Winther, M P J, additional

Published
2024
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5. A critical appreciation of pathway analysis in atherosclerotic disease. Cellular phenotypic plasticity as an illustrative example

Author

CDL Onderzoek Pasterkamp, Experimentele Afd. Cardiologie 1, Child Health, Circulatory Health, Onderzoek Vrouw Hart & Vaatziekten, Centraal Diagnostisch Laboratorium, Wesseling, M, Diez-Benavente, E, Mokry, M, den Ruijter, H M, Pasterkamp, G, CDL Onderzoek Pasterkamp, Experimentele Afd. Cardiologie 1, Child Health, Circulatory Health, Onderzoek Vrouw Hart & Vaatziekten, Centraal Diagnostisch Laboratorium, Wesseling, M, Diez-Benavente, E, Mokry, M, den Ruijter, H M, and Pasterkamp, G

Published
2024

8. Multi-omics integration identifies key upstream regulators of pathomechanisms in hypertrophic cardiomyopathy due to truncating MYBPC3 mutations

Author

Pei, J., Schuldt, M., Nagyova, E., Gu, Z., el Bouhaddani, S., Yiangou, L., Jansen, M., Calis, J. J. A., Dorsch, L. M., Blok, C. Snijders, van den Dungen, N. A. M., Lansu, N., Boukens, B. J., Efimov, I. R., Michels, M., Verhaar, M. C., de Weger, R., Vink, A., van Steenbeek, F. G., Baas, A. F., Davis, R. P., Uh, H. W., Kuster, D. W. D., Cheng, C., Mokry, M., van der Velden, J., Asselbergs, F. W., and Harakalova, M.

Published
2021
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9. Airway and Blood Monocyte Transcriptomic Profiling Reveals an Antiviral Phenotype in Infants With Severe Respiratory Syncytial Virus Infection.

Author

Chappin, K, Besteman, S B, Hennus, M P, Wildenbeest, J G, Mokry, M, Bont, L J, Vlist, M van der, Calis, J J A, and Investigators, PROMISE

Subjects
RESPIRATORY syncytial virus infections, HUMAN metapneumovirus infection, RESPIRATORY infections in children, RESPIRATORY infections, PHENOTYPES, PEDIATRIC intensive care
Abstract

Background Respiratory syncytial virus (RSV) infection is the primary cause of lower respiratory tract infections in children <5 years of age. Monocytes, especially in the respiratory tract, are suggested to contribute to RSV pathology, but their role is incompletely understood. With transcriptomic profiling of blood and airway monocytes, we describe the role of monocytes in severe RSV infection. Methods Tracheobronchial aspirates and blood samples were collected from control patients (n = 9) and those infected with RSV (n = 14) who were admitted to the pediatric intensive care unit. Monocytes (CD14+) were sorted and analyzed by RNA sequencing for transcriptomic profiling. Results Peripheral blood and airway monocytes of patients with RSV demonstrated increased expression of antiviral and interferon-responsive genes as compared with controls. Cytokine signaling showed a shared response between blood and airway monocytes while displaying responses that were more pronounced according to the tissue of origin. Airway monocytes upregulated additional genes related to migration and inflammation. Conclusions We found that the RSV-induced interferon response extends from the airways to the peripheral blood. Moreover, RSV induces a migration-promoting transcriptional program in monocytes. Unraveling the monocytic response and its role in the immune response to RSV infection could help the development of therapeutics to prevent severe disease. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Dilated Cardiomyopathy – Results, Conclusions and Perspectives

Author

Garnier, S, Harakalova, M, Weiss, S, Mokry, M, Isnard, R, Duboscq-Bidot, L, Komajda, M, Cambien, F, Deleuze, J-F, Dörr, M, Asselbergs F, W, Villard, E, Trégouët, D-A, Charron, P, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Utrecht University [Utrecht], Universität Greifswald - University of Greifswald, Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratory of Excellence GENMED [Paris] (Medical Genomics), University of Medicine Greifswald, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and GenMed consortuium

Subjects
[SDV]Life Sciences [q-bio]
Abstract

International audience

Published
2022

19. Thresholds of target phosphorus fertility classes in European fertilizer recommendations in relation to critical soil test phosphorus values derived from the analysis of 55 European long-term field experiments

Author

Steinfurth, K., Börjesson, G., Denoroy, P., Eichler-Löbermann, B., Gans, W., Heyn, J., Hirte, J., Huyghebaert, B., Jouany, C., Koch, D., Merbach, Ines, Mokry, M., Mollier, A., Morel, C., Panten, K., Peiter, E., Poulton, P.R., Reitz, Thomas, Holton Rubæk, G., Spiegel, H., van Laak, M., von Tucher, S., Buczko, U., Steinfurth, K., Börjesson, G., Denoroy, P., Eichler-Löbermann, B., Gans, W., Heyn, J., Hirte, J., Huyghebaert, B., Jouany, C., Koch, D., Merbach, Ines, Mokry, M., Mollier, A., Morel, C., Panten, K., Peiter, E., Poulton, P.R., Reitz, Thomas, Holton Rubæk, G., Spiegel, H., van Laak, M., von Tucher, S., and Buczko, U.

Abstract

Phosphorus (P) fertilizer recommendations of individual countries may differ in many aspects, but often the main principle is to reach or maintain a target range of plant-available P in soil. Within this target P fertility class, the soil is expected to supply enough P to the crop, while P fertilization replaces what is exported by the harvested crop. However, the threshold values of the target P fertility classes are based on a multitude of different soil test P (STP) methods and vary by a factor of up to three, even for countries using the same STP method. This study aimed to provide a comparison of the thresholds of target P fertility classes of different European countries and critical soil test P values (Pcrit; STP below which the average relative yield falls below 95% due to P insufficiency) derived from the analysis of data from 55 long-term field experiments in eight European countries. To overcome the issue of diverging STP methods, all values were converted to Olsen-P using empirically based conversion equations from the literature. Converted threshold values varied by a factor of up to five. For the experimental data, we fitted multi-level Mitscherlich-type models to determine Pcrit values of unfertilized soils corresponding to 95% of maximum yield. We found an average Olsen-Pcrit value of 15 mg P kg−1 (adj. R² = 0.37; RMSE = 14.1% relative yield; n = 2368; 55 experiments), which lies far below several country-specific thresholds of target P fertility classes. Crop-specific analyses resulted in higher Olsen-Pcrit values for sugar beet (22 mg P kg−1), potato (19 mg P kg−1) and winter rapeseed (18 mg P kg−1). Among the texture classes (loam, sand, silt and clay), sandy soils exhibited the highest average Olsen-Pcrit value (22 mg P kg−1). We consider a reevaluation of extraordinarily high country-specific thresholds as well as an inclusion of crop type and soil texture (where not already implemented) to be a reasonable measure towards more cost-effective and

Published
2022

20. Identification par étude d’association génome entier (GWAS) de deux nouveaux loci impliqués dans l’insuffisance cardiaque par cardiomyopathie dilatée en 3p25.1 et 22q11.23

Author

Garnier, S, Harakalova, M, Weiss, S, Mokry, M, Isnard, R, Duboscq-Bidot, L, Komajda, M, Cambien, F, Deleuze, J-F, Dörr, M, Asselbergs F, W, Villard, E, Trégouët, D-A, Charron, P, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Utrecht University [Utrecht], Universität Greifswald - University of Greifswald, Sorbonne Université (SU), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratory of Excellence GENMED [Paris] (Medical Genomics), University of Medicine Greifswald, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and SFGH

Subjects
[SDV]Life Sciences [q-bio]
Published
2022

26. Detection of two new DNA/chromatin regions increasing DCM risk

Author

Garnier, Sophie, Harakalova, M, Weiss, S, Mokry, M, Isnard, R, Duboscq-Bidot, L, Komajda, M, Dörr, M, Asselbergs F, W, Deleuze, J-F, Villard, E, Cambien, F, Trégouët, D-A, Charron, P, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Utrecht University [Utrecht], Universität Greifswald - University of Greifswald, Sorbonne Université (SU), University of Medicine Greifswald, Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratory of Excellence GENMED [Paris] (Medical Genomics), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

International audience

Published
2021

27. Epidurale Hirndruckmessung bei Kindern nach Herz-Kreislaufstillstand

Author

Trop, Marijy, Zobel, G., Grubbauer, H. M., Mokry, M., Lenz, Kurt, editor, Laggner, Anton N., editor, Deutsch, Erwin, editor, Binder, Heinrich, editor, Gadner, Helmut, editor, Grimm, Georg, editor, Kleinberger, Gunther, editor, Ritz, Rudolf, editor, Schuster, Hans Peter, editor, and Zaunschirm, Harald Andrew, editor

Published
1990
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28. Transcriptomic based clustering of advanced atherosclerotic plaques: Revisiting the lesion determinants that identify the vulnerable patient.

Author

Mokry, M., primary, Boltjes, A., additional, Van Der Laan, S.W., additional, Cui, K., additional, Slenders, L., additional, Benavente, E.D., additional, Van Den Dungen, N.A.M., additional, Timmerman, N., additional, De Kleijn, D.P.V., additional, Den Ruijter, H.M., additional, Miller, C., additional, Asselbergs, F.W., additional, and Pasterkamp, G., additional

Published
2021
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30. Sex-dependent gene regulation of human atherosclerotic plaques by DNA methylation and transcriptome integration points to smooth muscle cell involvement in women.

Author

Hartman, R., primary, Siemelink, M., additional, Haitjema, S., additional, Dekkers, K.F., additional, Slenders, L., additional, Boltjes, A., additional, Mokry, M., additional, Timmerman, N., additional, De Borst, G.J., additional, Heijmans, B.T., additional, Asselbergs, F.W., additional, Pasterkamp, G., additional, Van Der Laan, S.W., additional, and Den Ruijter, H.M., additional

Published
2021
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32. Proteomic and Functional Studies Reveal Detyrosinated Tubulin as Treatment Target in Sarcomere Mutation-Induced Hypertrophic Cardiomyopathy

Author

Schuldt, M. (Maike), Pei, J. (Jiayi), Harakalova, M. (Magdalena), Dorsch, L.M. (Larissa M.), Schlossarek, S. (Saskia), Mokry, M. (Michal), Knol, J.C. (Jaco), Pham, T.V. (Thang V.), Schelfhorst, T. (Tim), Piersma, S.R. (Sander R.), Dos Remedios, C. (Cris), Dalinghaus, M. (Michiel), Michels, M. (Michelle), Asselbergs, F.W. (Folkert W.), Moutin, M.-J. (Marie-Jo), Carrier, L. (Lucie), Jimenez, C.R. (Connie), Velden, J. (Jolanda) van der, Kuster, D.W.D. (Diederik), Schuldt, M. (Maike), Pei, J. (Jiayi), Harakalova, M. (Magdalena), Dorsch, L.M. (Larissa M.), Schlossarek, S. (Saskia), Mokry, M. (Michal), Knol, J.C. (Jaco), Pham, T.V. (Thang V.), Schelfhorst, T. (Tim), Piersma, S.R. (Sander R.), Dos Remedios, C. (Cris), Dalinghaus, M. (Michiel), Michels, M. (Michelle), Asselbergs, F.W. (Folkert W.), Moutin, M.-J. (Marie-Jo), Carrier, L. (Lucie), Jimenez, C.R. (Connie), Velden, J. (Jolanda) van der, and Kuster, D.W.D. (Diederik)

Abstract

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease. While ≈50% of patients with HCM carry a sarcomere gene mutation (sarcomere mutation-positive, HCMSMP), the genetic background is unknown in the other half of the patients (sarcomere mutation-negative, HCMSMN). Genotype-specific differences have been reported in cardiac function. Moreover, HCMSMN patients have later disease onset and a better prognosis than HCMSMP patients. To define if genotype-specific derailments at the protein level may explain the heterogeneity in disease development, we performed a proteomic analysis in cardiac tissue from a clinically well-phenotyped HCM patient group. METHODS: A proteomics screen was performed in cardiac tissue from 39 HCMSMP patients, 11HCMSMN patients, and 8 nonfailing controls. Patients with HCM had obstructive cardiomyopathy with left ventricular outflow tract obstruction and diastolic dysfunction. A novel MYBPC32373insG mouse model was used to confirm functional relevance of our proteomic findings. RESULTS: In all HCM patient samples, we found lower levels of metabolic pathway proteins and higher levels of extracellular matrix proteins. Levels of to

Published
2021
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33. Multi-omics integration identifies key upstream regulators of pathomechanisms in hypertrophic cardiomyopathy due to truncating MYBPC3 mutations

Author

Afd Pharmacoepi & Clinical Pharmacology, Interne geneeskunde GD, dCSCA AVR, Sub Inorganic Chemistry and Catalysis, LS Vertaalwetenschap, CS_Genetics, Pei, J, Schuldt, M, Nagyova, E, Gu, Z, El Bouhaddani, S, Yiangou, L, Jansen, M, Calis, J J A, Dorsch, L M, Blok, C Snijders, van den Dungen, N A M, Lansu, N, Boukens, B J, Efimov, I R, Michels, M, Verhaar, M C, de Weger, R, Vink, A, van Steenbeek, F G, Baas, A F, Davis, R P, Uh, H W, Kuster, D W D, Cheng, C, Mokry, M, van der Velden, J, Asselbergs, F W, Harakalova, M, Afd Pharmacoepi & Clinical Pharmacology, Interne geneeskunde GD, dCSCA AVR, Sub Inorganic Chemistry and Catalysis, LS Vertaalwetenschap, CS_Genetics, Pei, J, Schuldt, M, Nagyova, E, Gu, Z, El Bouhaddani, S, Yiangou, L, Jansen, M, Calis, J J A, Dorsch, L M, Blok, C Snijders, van den Dungen, N A M, Lansu, N, Boukens, B J, Efimov, I R, Michels, M, Verhaar, M C, de Weger, R, Vink, A, van Steenbeek, F G, Baas, A F, Davis, R P, Uh, H W, Kuster, D W D, Cheng, C, Mokry, M, van der Velden, J, Asselbergs, F W, and Harakalova, M

Published
2021

34. Multi-omics integration identifies key upstream regulators of pathomechanisms in hypertrophic cardiomyopathy due to truncating MYBPC3 mutations

Author

Onderzoek Precision medicine, Other research (not in main researchprogram), Biostatistiek Onderzoek, Genetica Klinische Genetica, Immuno/reuma onderzoek 5 (Vastert2), CMM Groep Cuppen, Unit Opleiding Aios, Nefro Vasculaire Geneeskunde, Circulatory Health, Regenerative Medicine and Stem Cells, Pathologie Laboratorium diagnostiek, Pathologie Pathologen staf, JC onderzoeksprogramma Methodologie, Onderzoek, Child Health, Team Medisch, Pei, J, Schuldt, M, Nagyova, E, Gu, Z, El Bouhaddani, S, Yiangou, L, Jansen, M, Calis, J J A, Dorsch, L M, Blok, C Snijders, van den Dungen, N A M, Lansu, N, Boukens, B J, Efimov, I R, Michels, M, Verhaar, M C, de Weger, R, Vink, A, van Steenbeek, F G, Baas, A F, Davis, R P, Uh, H W, Kuster, D W D, Cheng, C, Mokry, M, van der Velden, J, Asselbergs, F W, Harakalova, M, Onderzoek Precision medicine, Other research (not in main researchprogram), Biostatistiek Onderzoek, Genetica Klinische Genetica, Immuno/reuma onderzoek 5 (Vastert2), CMM Groep Cuppen, Unit Opleiding Aios, Nefro Vasculaire Geneeskunde, Circulatory Health, Regenerative Medicine and Stem Cells, Pathologie Laboratorium diagnostiek, Pathologie Pathologen staf, JC onderzoeksprogramma Methodologie, Onderzoek, Child Health, Team Medisch, Pei, J, Schuldt, M, Nagyova, E, Gu, Z, El Bouhaddani, S, Yiangou, L, Jansen, M, Calis, J J A, Dorsch, L M, Blok, C Snijders, van den Dungen, N A M, Lansu, N, Boukens, B J, Efimov, I R, Michels, M, Verhaar, M C, de Weger, R, Vink, A, van Steenbeek, F G, Baas, A F, Davis, R P, Uh, H W, Kuster, D W D, Cheng, C, Mokry, M, van der Velden, J, Asselbergs, F W, and Harakalova, M

Published
2021

35. Sex-dependent gene regulation of human atherosclerotic plaques by DNA methylation and transcriptome integration points to smooth muscle cell involvement in women

Author

Experimentele Afd. Cardiologie 1, Circulatory Health, CDL Arcadia, CDL Onderzoek Pasterkamp, Child Health, Infection & Immunity, Onderzoek Precision medicine, Zorgeenheid Vaatchirurgie Medisch, Brain, Regenerative Medicine and Stem Cells, Team Medisch, Centraal Diagnostisch Laboratorium, Onderzoek Vrouw Hart & Vaatziekten, Hartman, R., Siemelink, M., Haitjema, S., Dekkers, K. F., Slenders, L., Boltjes, A., Mokry, M., Timmerman, N., De Borst, G. J., Heijmans, B. T., Asselbergs, F. W., Pasterkamp, G., Van der Laan, S. W., Den Ruijter, H. M., Experimentele Afd. Cardiologie 1, Circulatory Health, CDL Arcadia, CDL Onderzoek Pasterkamp, Child Health, Infection & Immunity, Onderzoek Precision medicine, Zorgeenheid Vaatchirurgie Medisch, Brain, Regenerative Medicine and Stem Cells, Team Medisch, Centraal Diagnostisch Laboratorium, Onderzoek Vrouw Hart & Vaatziekten, Hartman, R., Siemelink, M., Haitjema, S., Dekkers, K. F., Slenders, L., Boltjes, A., Mokry, M., Timmerman, N., De Borst, G. J., Heijmans, B. T., Asselbergs, F. W., Pasterkamp, G., Van der Laan, S. W., and Den Ruijter, H. M.

Published
2021

36. Starve to Sustain - An Ancient Syrian Landrace of Sorghum as Tool for Phosphorous Bio-Economy?

Author

Kanbar, A., Mirzai, M., Abuslima, E., Flubacher, N., Eghbalian, R., Garbev, K., Bergfeldt, B., Ullrich, A., Leibold, H., Eiche, E., Müller, M., Mokry, M., Stapf, D., and Nick, P.

Subjects
Geography & travel, food and beverages, ddc:910
Abstract

Phosphorus (P) is an essential macronutrient, playing a role in developmental and metabolic processes in plants. To understand the local and systemic responses of sorghum to inorganic phosphorus (Pi) starvation and the potential of straw and ash for reutilisation in agriculture, we compared two grain (Razinieh) and sweet (Della) sorghum varieties with respect to their morpho-physiological and molecular responses. We found that Pi starvation increased the elongation of primary roots, the formation of lateral roots, and the accumulation of anthocyanin. In Razinieh, lateral roots were promoted to a higher extent, correlated with a higher expression of SbPht1 phosphate transporters. Infrared spectra of straw from mature plants raised to maturity showed two prominent bands at 1371 and 2337 cm−1, which could be assigned to P-H(H2) stretching vibration in phosphine acid and phosphinothious acid, and their derivates, whose abundance correlated with phosphate uptake of the source plant and genotype (with a higher intensity in Razinieh). The ash generated from these straws stimulated the shoot elongation and root development of the rice seedlings, especially for the material derived from Razinieh raised under Pi starvation. In conclusion, sorghum growing on marginal lands has potential as a bio-economy alternative for mineral phosphorus recycling.

Published
2021

39. Genome wide association analysis in dilated cardiomyopathy reveals two new key players in systolic heart failure on chromosomes 3p25.1 and 22q11.23

Author

Garnier, S, Harakalova, M, Weiss, S, Mokry, M, Isnard, R, Duboscq-Bidot, L, Komajda, M, Cambien, F, Deleuze, J-F, Dörr, M, Asselbergs F, W, Villard, E, Trégouët, D-A, Charron, P, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University Medical Center [Utrecht], Universität Greifswald - University of Greifswald, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Génomique cardiovasculaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratory of Excellence GENMED [Paris] (Medical Genomics), ICIN - Netherlands Heart Institute, University College of London [London] (UCL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), SFC, Utrecht University [Utrecht], Sorbonne Université (SU), Centre National de Recherche en Génomique Humaine (CNRGH), University of Medicine Greifswald, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)

Subjects
[SDV]Life Sciences [q-bio], Cardiology and Cardiovascular Medicine
Abstract

International audience

Published
2021

40. Association study and subsequent analyses revealed two new key players in DCM

Author

Garnier, S, Harakalova, M, Weiss, S, Mokry, M, Isnard, R, Duboscq-Bidot, L, Komajda, M, Cambien, F, Deleuze, J-F, Dörr, M, Asselbergs F, W, Villard, E, Trégouët, D-A, Charron, P, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Utrecht University [Utrecht], Universität Greifswald - University of Greifswald, Sorbonne Université (SU), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratory of Excellence GENMED [Paris] (Medical Genomics), University of Medicine Greifswald, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

International audience

Published
2020

41. Developmental programming in human umbilical cord vein endothelial cells following fetal growth restriction

Author

Terstappen, F. (Fieke), Calis, J.J.A. (Jorg J. A.), Paauw, N.D. (Nina D.), Joles, J.A. (Jaap), Rijn, B.B. (Bas) van, Mokry, M. (Michal), Plösch, T. (Torsten), Lely, A.T. (Titia), Terstappen, F. (Fieke), Calis, J.J.A. (Jorg J. A.), Paauw, N.D. (Nina D.), Joles, J.A. (Jaap), Rijn, B.B. (Bas) van, Mokry, M. (Michal), Plösch, T. (Torsten), and Lely, A.T. (Titia)

Abstract

Background: Fetal growth restriction (FGR) is associated with an increased susceptibility for various noncommunicable diseases in adulthood, including cardiovascular and renal disease. During FGR, reduced uteroplacental blood flow, oxygen and nutrient supply to the fetus are hypothesized to detrimentally influence cardiovascular and renal programming. This study examined whether developmental programming profiles, especially related to the cardiovascular and renal system, differ in human umbilical vein endothelial cells (HUVECs) collected from pregnancies complicated by placental insufficiency-induced FGR compared to normal growth pregnancies. Our approach, involving transcriptomic profiling by RNA-sequencing and gene set enrichment analysis focused on cardiovascular and renal gene sets and targeted DNA methylation assays, contributes to the identification of targets underlying long-term cardiovascular and renal diseases. Results: Gene set enrichment analysis showed several downregulated gene sets, most of them involved in immune or inflammatory pathways or cell cycle pathways. seven of the 22 significantly upregulated gene sets related to kidney development and four gene sets involved with cardiovascular health and function were downregulated in FGR (n = 11) versus control (n = 8). Transcriptomic profiling by RNA-sequencing revealed downregulated expression of LGALS1, FPR3 and NRM and upregulation of lincRNA RP5-855F14.1 in FGR compared to controls. DNA methylation was similar for LGALS1 between study groups, but relative hypomethylation of FPR3 and hypermethylation of NRM were present in FGR, especially in male offspring. Absolute differences in methylation were, however, small. Conclusion: This study showed upregulation of gene sets related to renal development in HUVECs collected from pregnancies complicated by FGR compared to control donors. The differentially expressed gene sets related to cardiovascular function and health might be in line with the downregula

Published
2020
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42. Prime editing for functional repair in patient-derived disease models

Author

Schene, IF, Joore, I.P., Oka, R., Mokry, M, van Vugt, A.H.M., Boxtel, R. (Ria) van, van der Doef, H.P.J., Laan, L.J.W. (Luc) van der, Verstegen, M.M.A. (Monique), Hasselt, P.M. (Peter) van, Nieuwenhuis, E.E.S. (Edward), Fuchs, SA, Schene, IF, Joore, I.P., Oka, R., Mokry, M, van Vugt, A.H.M., Boxtel, R. (Ria) van, van der Doef, H.P.J., Laan, L.J.W. (Luc) van der, Verstegen, M.M.A. (Monique), Hasselt, P.M. (Peter) van, Nieuwenhuis, E.E.S. (Edward), and Fuchs, SA

Published
2020
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44. H3K27ac acetylome signatures reveal the epigenomic reorganization in remodeled non-failing human hearts

Author

Pei, J. (Jiayi), Harakalova, M. (Magdalena), Treibel, T.A. (Thomas A.), Lumbers, R.T. (R Thomas), Boukens, B.J. (Bastiaan J.), Efimov, I.R. (Igor R.), van Dinter, J.T. (Jip T.), González, A. (Arantxa), López, B. (Begoña), El Azzouzi, H. (Hamid), van den Dungen, N. (Noortje), Van Dijk, C.G.M. (Christian G.M.), Krebber, M.M. (Merle M.), Ruijter, H.M. (Hester ) den, Pasterkamp, G. (Gerard), Duncker, D.J.G.M. (Dirk), Nieuwenhuis, E.E.S. (Edward), Weger, R.A. (Roel) de, Huibers, M.M. (Manon M.), Vink, A. (Ard), Moore, J.H. (Jason), Moon, J.C. (James C.), Verhaar, M.C. (Marianne), Kararigas, G. (Georgios), Mokry, M. (Michal), Asselbergs, F.W. (Folkert), Cheng, C. (Caroline), Pei, J. (Jiayi), Harakalova, M. (Magdalena), Treibel, T.A. (Thomas A.), Lumbers, R.T. (R Thomas), Boukens, B.J. (Bastiaan J.), Efimov, I.R. (Igor R.), van Dinter, J.T. (Jip T.), González, A. (Arantxa), López, B. (Begoña), El Azzouzi, H. (Hamid), van den Dungen, N. (Noortje), Van Dijk, C.G.M. (Christian G.M.), Krebber, M.M. (Merle M.), Ruijter, H.M. (Hester ) den, Pasterkamp, G. (Gerard), Duncker, D.J.G.M. (Dirk), Nieuwenhuis, E.E.S. (Edward), Weger, R.A. (Roel) de, Huibers, M.M. (Manon M.), Vink, A. (Ard), Moore, J.H. (Jason), Moon, J.C. (James C.), Verhaar, M.C. (Marianne), Kararigas, G. (Georgios), Mokry, M. (Michal), Asselbergs, F.W. (Folkert), and Cheng, C. (Caroline)

Abstract

BACKGROUND: H3K27ac histone acetylome changes contribute to the phenotypic response in heart diseases, particularly in end-stage heart failure. However, such epigenetic alterations have not been systematically investigated in remodeled non-failing human hearts. Therefore, valuable insight into cardiac dysfunction in early remodeling is lacking. This study aimed to reveal the acetylation changes of chromatin regions in response to myocardial remodeling and their correlations to transcriptional changes of neighboring genes. RESULTS: We detected chromatin regions with differential acetylation activity (DARs; Padj. < 0.05) between remodeled non-failing patient hearts and healthy donor hearts. The acetylation level of the chromatin region correlated with its RNA polymerase II occupancy level and the mRNA expression level of its adjacent gene per sample. Annotated genes from DARs were enriched in disease-related pathways, including fibrosis and cell metabolism regulation. DARs that change in the same direction have a tendency to cluster together, suggesting the well-reorganized chromatin architecture that facilitates the interactions of regulatory domains in response to myocardial remodeling. We further show the differences between the acetylation level and the mRNA expression level of cell-type-specific markers for cardiomyocytes and 11 non-myocyte cell types. Notably, we identified transcriptome factor (TF) binding motifs that were enriched in DARs and defined TFs that were predicted to bind to these motifs. We further showed 64 genes coding for these TFs that were differentially expressed in remodeled myocardium when compared with controls. CONCLUSIONS: Our study reveals extensive novel insight on myocardial remodeling at the DNA regulatory level. Differences between the acetylation level and the transcriptional level of cell-type-specific markers suggest additional mechanism(s) between acetylome and transcriptome. By integrating these two layers of epigenetic profiles

Published
2020
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47. H3K27ac acetylome signatures reveal the epigenomic reorganization in remodeled non-failing human hearts

Author

Pei, JY, Harakalova, M, Treibel, TA, Lumbers, RT, Boukens, BJ, Efimov, IR, van Dinter, JT, Gonzalez, A, Lopez, B, el Azzouzi, H, van den Dungen, N, van Dijk, CGM, Krebber, M M, den Ruijter, HM, Pasterkamp, G, Duncker, Dirk-jan, Nieuwenhuis, EES, de Weger, R, Huibers, MMH, Vink, A, Moore, JH, Moon, JC, Verhaar, MC, Kararigas, G, Mokry, M, Asselbergs, FW, Cheng, Caroline, Pei, JY, Harakalova, M, Treibel, TA, Lumbers, RT, Boukens, BJ, Efimov, IR, van Dinter, JT, Gonzalez, A, Lopez, B, el Azzouzi, H, van den Dungen, N, van Dijk, CGM, Krebber, M M, den Ruijter, HM, Pasterkamp, G, Duncker, Dirk-jan, Nieuwenhuis, EES, de Weger, R, Huibers, MMH, Vink, A, Moore, JH, Moon, JC, Verhaar, MC, Kararigas, G, Mokry, M, Asselbergs, FW, and Cheng, Caroline

Published
2020

49. Genome wide association analysis in dilated cardiomyopathy revealed two new susceptibility loci for systolic heart failure

Author

Garnier, S, primary, Harakalova, M, additional, Weiss, S, additional, Mokry, M, additional, Van Setten, J, additional, Proust, C, additional, Duboscq-Bidot, L, additional, Boland, A, additional, Deleuze, J.-F, additional, Dorr, M, additional, Asselbergs, F.-W, additional, Cambien, F, additional, Villard, E, additional, Tregouet, D.-A, additional, and Charron, P, additional

Published
2020
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