Transcriptomic-based clustering of human atherosclerotic plaques identifies subgroups with different underlying biology and clinical presentation.

Autor: Mokry M; Central Diagnostics Laboratory, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands.; Laboratory of Experimental Cardiology, Department of Cardiology, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands., Boltjes A; Central Diagnostics Laboratory, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands., Slenders L; Central Diagnostics Laboratory, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands., Bel-Bordes G; Central Diagnostics Laboratory, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands., Cui K; Laboratory of Experimental Cardiology, Department of Cardiology, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands., Brouwer E; Central Diagnostics Laboratory, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands., Mekke JM; Department of Vascular Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands., Depuydt MAC; Leiden Academic Centre for Drug Research, Division of Biotherapeutics, Leiden University, Leiden, The Netherlands., Timmerman N; Department of Vascular Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands., Waissi F; Department of Vascular Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands., Verwer MC; Department of Vascular Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands., Turner AW; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA., Khan MD; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA., Hodonsky CJ; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA., Benavente ED; Laboratory of Experimental Cardiology, Department of Cardiology, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands., Hartman RJG; Laboratory of Experimental Cardiology, Department of Cardiology, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands., van den Dungen NAM; Central Diagnostics Laboratory, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands., Lansu N; Central Diagnostics Laboratory, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands., Nagyova E; Central Diagnostics Laboratory, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands., Prange KHM; Amsterdam University Medical Centers - location AMC, University of Amsterdam, Experimental Vascular Biology, Department of Medical Biochemistry, Amsterdam Cardiovascular Sciences, Amsterdam Infection and Immunity, Amsterdam, The Netherlands., Kovacic JC; Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Victor Chang Cardiac Research Institute, Darlinghurst, Australia; and St Vincent's Clinical School, University of New South Wales, Australia., Björkegren JLM; Department of Medicine, Karolinska Institutet, Karolinska Universitetssjukhuset, Huddinge, Sweden.; Department of Genetics & Genomic Sciences, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029-6574, USA., Pavlos E; Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece., Andreakos E; Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece., Schunkert H; Department of Cardiology, German Heart Centre Munich, Technical University of Munich, Munich, Germany.; German Centre for Cardiovascular Research (DZHK e.V.), Partner Site Munich Heart Alliance, Munich, Germany., Owens GK; Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA.; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA, USA., Monaco C; Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford., Finn AV; CVPath Institute, Inc, Gaithersburg, MD, USA., Virmani R; CVPath Institute, Inc, Gaithersburg, MD, USA., Leeper NJ; Department of Surgery, Division of Vascular Surgery, Stanford University School of Medicine, Stanford, CA., de Winther MPJ; Amsterdam University Medical Centers - location AMC, University of Amsterdam, Experimental Vascular Biology, Department of Medical Biochemistry, Amsterdam Cardiovascular Sciences, Amsterdam Infection and Immunity, Amsterdam, The Netherlands., Kuiper J; Leiden Academic Centre for Drug Research, Division of Biotherapeutics, Leiden University, Leiden, The Netherlands., de Borst GJ; Department of Vascular Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands., Stroes ESG; Department of Vascular Medicine, Amsterdam University Medical Centers, Location AMC, Amsterdam, the Netherlands., Civelek M; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA., de Kleijn DPV; Department of Vascular Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands., den Ruijter HM; Laboratory of Experimental Cardiology, Department of Cardiology, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands., Asselbergs FW; Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.; Health Data Research UK and Institute of Health Informatics, University College London, London, United Kingdom., van der Laan SW; Central Diagnostics Laboratory, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands., Miller CL; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.; Department of Biomedical Engineering, Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA.; Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA., Pasterkamp G; Central Diagnostics Laboratory, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands.
Jazyk: angličtina
Zdroj: Nature cardiovascular research [Nat Cardiovasc Res] 2022 Dec; Vol. 1 (12), pp. 1140-1155. Date of Electronic Publication: 2022 Dec 12.
DOI: 10.1038/s44161-022-00171-0
Abstrakt: Histopathological studies have revealed key processes of atherosclerotic plaque thrombosis. However, the diversity and complexity of lesion types highlight the need for improved sub-phenotyping. Here we analyze the gene expression profiles of 654 advanced human carotid plaques. The unsupervised, transcriptome-driven clustering revealed five dominant plaque types. These plaque phenotypes were associated with clinical presentation and showed differences in cellular compositions. Validation in coronary segments showed that the molecular signature of these plaques was linked to coronary ischemia. One of the plaque types with the most severe clinical symptoms pointed to both inflammatory and fibrotic cell lineages. Further, we did a preliminary analysis of potential circulating biomarkers that mark the different plaques phenotypes. In conclusion, the definition of the plaque at risk for a thrombotic event can be fine-tuned by in-depth transcriptomic-based phenotyping. These differential plaque phenotypes prove clinically relevant for both carotid and coronary artery plaques and point to distinct underlying biology of symptomatic lesions.
Competing Interests: CLM has received funding support from AstraZeneca for work unrelated to this study. GP received funding support from Roche to partly cover the generation of biomarker data. The remaining authors declare no competing interests.
Databáze: MEDLINE
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