Transcriptomic and spatial dissection of human ex vivo right atrial tissue reveals proinflammatory microvascular changes in ischemic heart disease
Suvi Linna-Kuosmanen, Eloi Schmauch, Kyriakitsa Galani, Johannes Ojanen, Carles A. Boix, Tiit Örd, Anu Toropainen, Prosanta Singha, Pierre R. Moreau, Kristiina Harju, Adriana Blazeski, Åsa Segerstolpe, Veikko Lahtinen, Lei Hou, Kai Kang, Elamaran Meibalan, Leandro Z. Agudelo, Hannu Kokki, Jari Halonen, Juho Jalkanen, Jarmo Gunn, Calum A. MacRae, Maija Hollmén, Juha Hartikainen, Minna U. Kaikkonen, Guillermo García‐Cardeña, Pasi Tavi, Tuomas Kiviniemi, Manolis Kellis
Abstract
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.