Ischemic heart disease and heart failure are associated with previously unknown changes in the right atrium of the heart, a new study shows. The groundbreaking study reveals how various forms of heart disease drive changes in the right atrial tissue and pericardial fluid, potentially contributing to the disease progression.
Cardiovascular disease has profound effects on the structure and function of the heart. While past research has mainly focused on the left ventricle and the coronary arteries, the effects of the disease on the right atrium remain largely unexplored.
Right atrium functions as the entryway to the heart, pushing blood towards right ventricle and the lungs. It also houses the pacemaker of the heart, the sinoatrial node, that initiates and maintains the heartbeat. For this reason, pathological remodeling of the site may have serious consequences, including sinus node dysfunction and arrhythmias, or increased risk of heart failure and sudden death.
Microvasculature consists of small vessels that as a network regulate blood perfusion and conduct exchange between the blood and tissue. Several studies have suggested that dysfunction of this microvasculature is an underlying factor in major cardiovascular diseases and shown an association to more advanced disease and worse disease outcomes. However, the lack of tools for studying cellular and molecular changes in the microvasculature has left the mechanisms unexplored in human disease.
In a pioneering effort, published in Cell Reports Medicine, a team of researchers from the Massachusetts Institute of Technology (MIT), Harvard Medical School, University of Turku, and University of Eastern Finland, developed methods for studying the gene expression changes in the microvascular cells and their surrounding tissue at single-cell and subcellular resolutions. These methods are applicable beyond cardiac tissue and heart disease, providing broader utility for them.
The study mapped mechanistic changes across right atrial tissue samples collected during open-heart surgeries in two prospective studies at the Kuopio and Turku University Hospitals, and included patients with ischemic heart disease, myocardial infarction, and both ischemic and non-ischemic heart failure, using asymptomatic patients with valvular disease as the control group.
The results of the study highlighted metabolic reprogramming, microvascular dysfunction, and a presence of pro-inflammatory molecules in the right atrial tissue, potentially due to a systemic inflammatory response that may initiate and promote pathological changes in the target tissue. Further analysis identified several potential therapeutic target molecules, such as IL-1β and IL-6, whose inhibition could mitigate inflammation and prevent the severe cardiovascular remodeling occurring in disease progression.
“These findings underscore the importance of investigating all functionally relevant parts of the heart to fully understand the mechanisms that promote severe cardiovascular disease. Expanding the focus of cardiovascular research beyond well-known sites such as the atherosclerotic plaques and left ventricle could unveil critical drivers of the diseases and inform new therapeutic strategies,” says the study director Suvi Linna-Kuosmanen, Vice Chair of the Metabolic Diseases research community at the University of Eastern Finland.
Through dissection of the gene expression changes in the right atrium, the study provides a snapshot into the molecular mechanisms underlying major cardiovascular diseases. These insights could pave the way for novel treatments and preventive measures aimed at arrhythmias, heart failure, and sudden death. Follow-up studies are underway at the A.I. Virtanen Institute, University of Eastern Finland.
The project was funded by the Academy of Finland, Clinical Research Fund (EVO) of Turku University Hospital, European Research Council, Finnish Foundation for Cardiovascular Research, Finnish Medical Foundation, Saastamoinen Foundation, Sigrid Jusélius Foundation, Orion Research Foundation, Yrjö Jahnsson Foundation, and the National Institutes of Health (NIH).
For more information, please contact the study director Suvi Linna-Kuosmanen, https://uefconnect.uef.fi/en/person/suvi.linna-kuosmanen/
Research article (Open Access):
Linna-Kuosmanen et al. Transcriptomic and spatial dissection of human ex vivo right atrial tissue reveals proinflammatory microvascular changes in ischemic heart disease. Cell Reports Medicine 5, 101556, May 21, 2024. DOI: https://doi.org/10.1016/j.xcrm.2024.101556
