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1,379 results on '"Borén, JAN"'

4. Integrative proteo-transcriptomic characterization of advanced fibrosis in chronic liver disease across etiologies

Author

Yang, Hong, Atak, Dila, Yuan, Meng, Li, Mengzhen, Altay, Ozlem, Demirtas, Elif, Peltek, Ibrahim Batuhan, Ulukan, Burge, Yigit, Buket, Sipahioglu, Tarik, Álvez, María Bueno, Meng, Lingqi, Yüksel, Bayram, Turkez, Hasan, Kirimlioglu, Hale, Saka, Burcu, Yurdaydin, Cihan, Akyildiz, Murat, Dayangac, Murat, Uhlen, Mathias, Boren, Jan, Zhang, Cheng, Mardinoglu, Adil, and Zeybel, Mujdat

Published
2025
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14. Intussusceptive Angiogenesis in Human Metastatic Malignant Melanoma

Author

Pandita, Ankur, Ekstrand, Matias, Bjursten, Sara, Zhao, Zhiyuan, Fogelstrand, Per, Le Gal, Kristell, Ny, Lars, Bergo, Martin O, Karlsson, Joakim, Nilsson, Jonas A, Akyürek, Levent M, Levin, Malin C, Borén, Jan, Ewald, Andrew J, Mostov, Keith E, and Levin, Max

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Biotechnology, Genetics, Cancer, 5.1 Pharmaceuticals, Aged, Aged, 80 and over, Animals, Female, Heterografts, Humans, Male, Matrix Metalloproteinase 9, Melanoma, Mice, Middle Aged, Neovascularization, Pathologic, Skin Neoplasms, Melanoma, Cutaneous Malignant, Medical and Health Sciences, Pathology, Biomedical and clinical sciences, Health sciences
Abstract

Angiogenesis supplies oxygen and nutrients to growing tumors. Inhibiting angiogenesis may stop tumor growth, but vascular endothelial growth factor inhibitors have limited effect in most tumors. This limited effect may be explained by an additional, less vascular endothelial growth factor-driven form of angiogenesis known as intussusceptive angiogenesis. The importance of intussusceptive angiogenesis in human tumors is not known. Epifluorescence and confocal microscopy was used to visualize intravascular pillars, the hallmark structure of intussusceptive angiogenesis, in tumors. Human malignant melanoma metastases, patient-derived melanoma xenografts in mice (PDX), and genetically engineered v-raf murine sarcoma viral oncogene homolog B1 (BRAF)-induced, phosphatase and TENsin homolog deleted on chromosome 10 (PTEN)-deficient (BPT) mice (BrafCA/+Ptenf/fTyr-Cre+/0-mice) were analyzed for pillars. Gene expression in human melanoma metastases and PDXs was analyzed by RNA sequencing. Matrix metalloproteinase 9 (MMP9) protein expression and T-cell and macrophage infiltration in tumor sections were determined with multiplex immunostaining. Intravascular pillars were detected in human metastases but rarely in PDXs and not in BPT mice. The expression of MMP9 mRNA was higher in human metastases compared with PDXs. High expression of MMP9 protein as well as infiltration of macrophages and T-cells were detected in proximity to intravascular pillars. MMP inhibition blocked formation of pillars, but not tubes or tip cells, in vitro. In conclusion, intussusceptive angiogenesis may contribute to the growth of human melanoma metastases. MMP inhibition blocked pillar formation in vitro and should be further investigated as a potential anti-angiogenic drug target in metastatic melanoma.

Published
2021

17. Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial

Author

Yulug, Burak, Altay, Ozlem, Li, Xiangyu, Hanoglu, Lutfu, Cankaya, Seyda, Lam, Simon, Velioglu, Halil Aziz, Yang, Hong, Coskun, Ebru, Idil, Ezgi, Nogaylar, Rahim, Ozsimsek, Ahmet, Bayram, Cemil, Bolat, Ismail, Oner, Sena, Tozlu, Ozlem Ozdemir, Arslan, Mehmet Enes, Hacimuftuoglu, Ahmet, Yildirim, Serkan, Arif, Muhammad, Shoaie, Saeed, Zhang, Cheng, Nielsen, Jens, Turkez, Hasan, Borén, Jan, Uhlén, Mathias, and Mardinoglu, Adil

Published
2023
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22. Metabolism of Triglyceride-Rich Lipoproteins

Author

Borén, Jan, Taskinen, Marja-Riitta, Barrett, James E., Editor-in-Chief, Flockerzi, Veit, Editorial Board Member, Frohman, Michael A., Editorial Board Member, Geppetti, Pierangelo, Editorial Board Member, Hofmann, Franz B., Editorial Board Member, Kuner, Rohini, Editorial Board Member, Michel, Martin C., Editorial Board Member, Page, Clive P., Editorial Board Member, Wang, KeWei, Editorial Board Member, von Eckardstein, Arnold, editor, and Binder, Christoph J., editor

Published
2022
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26. Whole genome sequencing in early onset advanced heart failure.

Author

Linnér, Erik, Czuba, Tomasz, Gidlöf, Olof, Lundgren, Jakob, Bollano, Entela, Hellberg, Maria, Celik, Selvi, Pimpalwar, Neha, Rentzsch, Philipp, Martorella, Molly, Gummesson, Anders, Melander, Olle, Albinsson, Sebastian, Dellgren, Göran, Borén, Jan, Jeppsson, Anders, Lumbers, R. Thomas, Shah, Sonia, Nilsson, Johan, and Natarajan, Pradeep

Subjects
WHOLE genome sequencing, GENETIC testing, GENETIC variation, HEART failure, HEART transplant recipients
Abstract

The genetic contributions to early onset heart failure (HF) are incompletely understood. Genetic testing in advanced HF patients undergoing heart transplantation (HTx) may yield clinical benefits, but data is limited. We performed deep-coverage whole genome sequencing (WGS) in 102 Swedish HTx recipients. Gene lists were compiled through a systematic literature review. Variants were prioritized for pathogenicity and classified manually. We also compared polygenic HF risk scores to a population-based cohort. We found a pathogenic (LP/P) variant in 34 individuals (34%). Testing yield was highest in hypertrophic (63% LP/P carriers), dilated (40%) and arrhythmogenic right ventricular (33%) cardiomyopathy and lower in ischemic cardiomyopathy (10%). A family history was more common in LP/P variant carriers than in non-carriers but was present in less than half of carriers (44% vs 13%, P < 0.001), whereas age was similar. Polygenic risk scores were similar in HTx recipients and the population cohort. In conclusion, we observed a high prevalence of pathogenic cardiomyopathy gene variants in individuals with early-onset advanced HF, which could not accurately be ruled out by family history and age. In contrast, we did not observe higher polygenic risk scores in early onset advanced HF cases than in the general population. [ABSTRACT FROM AUTHOR]

Published
2025
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27. Testosterone exacerbates neutrophilia and cardiac injury in myocardial infarction via actions in bone marrow.

Author

Svedlund Eriksson, Elin, Lantero Rodriguez, Marta, Halvorsen, Bente, Johansson, Inger, Mårtensson, Anna K. F., Wilhelmson, Anna S., Huse, Camilla, Ueland, Thor, Aukrust, Pål, Broch, Kaspar, Gullestad, Lars, Amundsen, Brage Høyem, Andersen, Geir Øystein, Karlsson, Mikael C. I., Hagberg Thulin, Malin, Camponeschi, Alessandro, Trompet, Dana, Hammarsten, Ola, Redfors, Björn, and Borén, Jan

Subjects
ANDROGEN receptors, INTERLEUKIN-6 receptors, MEDICAL sciences, MYOCARDIAL infarction, BONE marrow
Abstract

Men develop larger infarct sizes than women after a myocardial infarction (MI), but the mechanism underlying this sex difference is unknown. Here, we demonstrated that blood neutrophil counts post-MI were higher in male than female mice. Castration-induced testosterone deficiency reduced blood neutrophil counts to the level in females and increased survival post-MI. These effects were mimicked by Osterix-directed ablation of the androgen receptor in bone marrow (BM). Mechanistically, androgens downregulated the leukocyte retention factor CXCL12 in BM stromal cells. Post-hoc analysis of clinical trial data showed that neutrophilia was greater in men than women after reperfusion of first-time ST-elevation MI, and tocilizumab, an interleukin-6 receptor inhibitor, reduced blood neutrophil counts and infarct size to a greater extent in men than women. Our work reveals a previously unknown mechanism connecting testosterone with neutrophilia and MI injury via BM and identifies the importance of considering sex when developing anti-inflammatory strategies to treat MI. Men develop larger myocardial infarction (MI) sizes than women. Here, the authors show that male sex and testosterone, via bone marrow stroma, exacerbates MI-induced neutrophilia and cardiac injury and that response to anti-inflammatory treatment in MI is greater in men than women [ABSTRACT FROM AUTHOR]

Published
2025
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38. Family-specific aggregation of lipid GWAS variants confers the susceptibility to familial hypercholesterolemia in a large Austrian family

Author

Nikkola, Elina, Ko, Arthur, Alvarez, Marcus, Cantor, Rita M, Garske, Kristina, Kim, Elliot, Gee, Stephanie, Rodriguez, Alejandra, Muxel, Reinhard, Matikainen, Niina, Söderlund, Sanni, Motazacker, Mahdi M, Borén, Jan, Lamina, Claudia, Kronenberg, Florian, Schneider, Wolfgang J, Palotie, Aarno, Laakso, Markku, Taskinen, Marja-Riitta, and Pajukanta, Päivi

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Digestive Diseases, Human Genome, Prevention, Genetics, Heart Disease, Cardiovascular, Atherosclerosis, Aetiology, 2.1 Biological and endogenous factors, Apolipoprotein B-100, Austria, Biomarkers, Cholesterol, DNA Mutational Analysis, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Heredity, Humans, Hyperlipoproteinemia Type II, Lipoprotein(a), Male, Middle Aged, Mutation, Pedigree, Phenotype, Polymorphism, Single Nucleotide, Receptors, LDL, Risk Factors, Exome Sequencing, Familial hypercholesterolemia, LDL cholesterol, Genetic risk score, Lipoprotein, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

Background and aimsHypercholesterolemia confers susceptibility to cardiovascular disease (CVD). Both serum total cholesterol (TC) and LDL-cholesterol (LDL-C) exhibit a strong genetic component (heritability estimates 0.41-0.50). However, a large part of this heritability cannot be explained by the variants identified in recent extensive genome-wide association studies (GWAS) on lipids. Our aim was to find genetic causes leading to high LDL-C levels and ultimately CVD in a large Austrian family presenting with what appears to be autosomal dominant inheritance for familial hypercholesterolemia (FH).MethodsWe utilized linkage analysis followed by whole-exome sequencing and genetic risk score analysis using an Austrian multi-generational family with various dyslipidemias, including elevated TC and LDL-C, and one family branch with elevated lipoprotein (a) (Lp(a)).ResultsWe did not find evidence for genome-wide significant linkage for LDL-C or apparent causative variants in the known FH genes rather, we discovered a particular family-specific combination of nine GWAS LDL-C SNPs (p = 0.02 by permutation), and putative less severe familial hypercholesterolemia mutations in the LDLR and APOB genes in a subset of the affected family members. Separately, high Lp(a) levels observed in one branch of the family were explained primarily by the LPA locus, including short (

Published
2017

39. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel

Author

Ference, Brian A, Ginsberg, Henry N, Graham, Ian, Ray, Kausik K, Packard, Chris J, Bruckert, Eric, Hegele, Robert A, Krauss, Ronald M, Raal, Frederick J, Schunkert, Heribert, Watts, Gerald F, Borén, Jan, Fazio, Sergio, Horton, Jay D, Masana, Luis, Nicholls, Stephen J, Nordestgaard, Børge G, van de Sluis, Bart, Taskinen, Marja-Riitta, Tokgözoğlu, Lale, Landmesser, Ulf, Laufs, Ulrich, Wiklund, Olov, Stock, Jane K, Chapman, M John, and Catapano, Alberico L

Subjects
Cardiovascular, Atherosclerosis, Clinical Trials and Supportive Activities, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Anticholesteremic Agents, Cholesterol, HDL, Cholesterol, LDL, Consensus, Epidemiologic Methods, Ezetimibe, Genetic Predisposition to Disease, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hyperlipidemias, Lipoproteins, LDL, PCSK9 Inhibitors, Cardiovascular disease, Causality, Clinical trials, Low-density lipoprotein, Mendelian randomization, PCSK9, Recommendations, Statin, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Cardiovascular System & Hematology
Abstract

AimsTo appraise the clinical and genetic evidence that low-density lipoproteins (LDLs) cause atherosclerotic cardiovascular disease (ASCVD).Methods and resultsWe assessed whether the association between LDL and ASCVD fulfils the criteria for causality by evaluating the totality of evidence from genetic studies, prospective epidemiologic cohort studies, Mendelian randomization studies, and randomized trials of LDL-lowering therapies. In clinical studies, plasma LDL burden is usually estimated by determination of plasma LDL cholesterol level (LDL-C). Rare genetic mutations that cause reduced LDL receptor function lead to markedly higher LDL-C and a dose-dependent increase in the risk of ASCVD, whereas rare variants leading to lower LDL-C are associated with a correspondingly lower risk of ASCVD. Separate meta-analyses of over 200 prospective cohort studies, Mendelian randomization studies, and randomized trials including more than 2 million participants with over 20 million person-years of follow-up and over 150 000 cardiovascular events demonstrate a remarkably consistent dose-dependent log-linear association between the absolute magnitude of exposure of the vasculature to LDL-C and the risk of ASCVD; and this effect appears to increase with increasing duration of exposure to LDL-C. Both the naturally randomized genetic studies and the randomized intervention trials consistently demonstrate that any mechanism of lowering plasma LDL particle concentration should reduce the risk of ASCVD events proportional to the absolute reduction in LDL-C and the cumulative duration of exposure to lower LDL-C, provided that the achieved reduction in LDL-C is concordant with the reduction in LDL particle number and that there are no competing deleterious off-target effects.ConclusionConsistent evidence from numerous and multiple different types of clinical and genetic studies unequivocally establishes that LDL causes ASCVD.

Published
2017

43. APRIL limits atherosclerosis by binding to heparan sulfate proteoglycans

Author

Tsiantoulas, Dimitrios, Eslami, Mahya, Obermayer, Georg, Clement, Marc, Smeets, Diede, Mayer, Florian J., Kiss, Máté G., Enders, Lennart, Weißer, Juliane, Göderle, Laura, Lambert, Jordi, Frommlet, Florian, Mueller, André, Hendrikx, Tim, Ozsvar-Kozma, Maria, Porsch, Florentina, Willen, Laure, Afonyushkin, Taras, Murphy, Jane E., Fogelstrand, Per, Donzé, Olivier, Pasterkamp, Gerard, Hoke, Matthias, Kubicek, Stefan, Jørgensen, Helle F., Danchin, Nicolas, Simon, Tabassome, Scharnagl, Hubert, März, Winfried, Borén, Jan, Hess, Henry, Mallat, Ziad, Schneider, Pascal, and Binder, Christoph J.

Published
2021
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45. Targeting CD38 with monoclonal antibodies disrupts key survival pathways in paediatric Burkitt's lymphoma malignant B cells.

Author

Kläsener, Kathrin, Herrmann, Nadja, Håversen, Liliana, Sundell, Timothy, Sundqvist, Martina, Lundqvist, Christina, Manna, Paul T, Jonsson, Charlotte A, Visentini, Marcella, Ljung Sass, Diana, McGrath, Sarah, Grimstad, Kristoffer, Aranburu, Alaitz, Mellgren, Karin, Fogelstrand, Linda, Forsman, Huamei, Ekwall, Olov, Borén, Jan, Gjertsson, Inger, and Reth, Michael

Subjects
BURKITT'S lymphoma, B cell lymphoma, METABOLIC reprogramming, MEMBRANE proteins, CELL proliferation
Abstract

Objectives: Paediatric Burkitt's lymphoma (pBL) is the most common childhood non‐Hodgkin B‐cell lymphoma. Despite the encouraging survival rates for most children, treating cases with relapse/resistance to current therapies remains challenging. CD38 is a transmembrane protein highly expressed in pBL. This study investigates the effectiveness of CD38‐targeting monoclonal antibodies (mAbs), daratumumab and isatuximab, in impairing crucial cellular processes and survival pathways in pBL malignant cells. Methods: In silico analyses of patient samples, combined with in vitro experiments using the Ramos cell line, were conducted to assess the impact of daratumumab and isatuximab on cellular proliferation, apoptosis and the phosphoinositide 3‐kinase (PI3K) pathway. Results: Isatuximab was found to be more effective than daratumumab in disrupting B‐cell receptor signalling, reducing cellular proliferation and inducing apoptosis. Additionally, isatuximab caused a significant impairment of the PI3K pathway and induced metabolic reprogramming in pBL cells. The study also revealed a correlation between CD38 and MYC expression levels in pBL patient samples, suggesting CD38 involvement in key oncogenic processes. Conclusion: The study emphasises the therapeutic potential of CD38‐targeting mAbs, particularly isatuximab, in pBL. [ABSTRACT FROM AUTHOR]

Published
2024
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