Transcriptomic and spatial dissection of human ex vivo right atrial tissue reveals proinflammatory microvascular changes in ischemic heart disease.

Autor:	Linna-Kuosmanen S; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland. Electronic address: suvi.linna-kuosmanen@uef.fi., Schmauch E; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland., Galani K; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Ojanen J; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland., Boix CA; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Örd T; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland., Toropainen A; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland., Singha PK; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland., Moreau PR; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland., Harju K; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland., Blazeski A; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA., Segerstolpe Å; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Lahtinen V; Heart Center, Turku University Hospital, 20521 Turku, Finland; MediCity Research Laboratories and InFLAMES Flagship, University of Turku, 20500 Turku, Finland., Hou L; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Kang K; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Meibalan E; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA., Agudelo LZ; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Kokki H; School of Medicine, University of Eastern Finland, 70211 Kuopio, Finland., Halonen J; School of Medicine, University of Eastern Finland, 70211 Kuopio, Finland; Heart Center, Kuopio University Hospital, 70200 Kuopio, Finland., Jalkanen J; MediCity Research Laboratories and InFLAMES Flagship, University of Turku, 20500 Turku, Finland., Gunn J; Heart Center, Turku University Hospital, 20521 Turku, Finland; Department of Medicine, University of Turku, 20500 Turku, Finland., MacRae CA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Cardiovascular Medicine and Network Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA., Hollmén M; MediCity Research Laboratories and InFLAMES Flagship, University of Turku, 20500 Turku, Finland., Hartikainen JEK; School of Medicine, University of Eastern Finland, 70211 Kuopio, Finland; Heart Center, Kuopio University Hospital, 70200 Kuopio, Finland., Kaikkonen MU; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland., García-Cardeña G; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA., Tavi P; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland., Kiviniemi T; Heart Center, Turku University Hospital, 20521 Turku, Finland; Department of Medicine, University of Turku, 20500 Turku, Finland; Cardiovascular Medicine and Network Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Kellis M; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: manoli@mit.edu.
Jazyk:	angličtina
Zdroj:	Cell reports. Medicine [Cell Rep Med] 2024 May 21; Vol. 5 (5), pp. 101556.
DOI:	10.1016/j.xcrm.2024.101556
Abstrakt:	Cardiovascular disease plays a central role in the electrical and structural remodeling of the right atrium, predisposing to arrhythmias, heart failure, and sudden death. Here, we dissect with single-nuclei RNA sequencing (snRNA-seq) and spatial transcriptomics the gene expression changes in the human ex vivo right atrial tissue and pericardial fluid in ischemic heart disease, myocardial infarction, and ischemic and non-ischemic heart failure using asymptomatic patients with valvular disease who undergo preventive surgery as the control group. We reveal substantial differences in disease-associated gene expression in all cell types, collectively suggesting inflammatory microvascular dysfunction and changes in the right atrial tissue composition as the valvular and vascular diseases progress into heart failure. The data collectively suggest that investigation of human cardiovascular disease should expand to all functionally important parts of the heart, which may help us to identify mechanisms promoting more severe types of the disease. Competing Interests: Declaration of interests Authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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