The electrical and structural remodeling of the right atrium, which increases the risk of arrhythmias, heart failure, and sudden death, is mainly influenced by cardiovascular illness.
The right atrium is the heart’s entrance, forcing blood into the right ventricle and the lungs. It also contains the sinoatrial node, the heart’s pacemaker, which starts and keeps the heartbeat going. Thus, pathological remodeling of the location may result in significant complications such as arrhythmias and malfunction of the sinus nodes or elevated risk of heart failure and abrupt death.
The microvasculature, a network of minuscule vessels, regulates blood perfusion and promotes blood-tissue interaction. Several investigations have discovered an underlying cause of major cardiovascular disorders and a connection between the failure of this microvasculature and worse disease outcomes.
Nonetheless, the mechanisms underlying human disease remain unknown due to insufficient instruments for examining cellular and molecular alterations in the microvasculature.
Researchers from the Massachusetts Institute of Technology (MIT), Harvard Medical School, the University of Turku, and the University of Eastern Finland developed novel techniques for examining changes in gene expression in microvascular cells and the surrounding tissue at single-cell and subcellular resolutions. These techniques have broader applicability and are not limited to cardiac tissue and heart disease.
Two prospective studies conducted at the Kuopio and Turku University Hospitals mapped mechanistic changes across right atrial tissue samples obtained during open-heart surgeries. The study comprised individuals with myocardial infarction, ischemic and non-ischemic heart failure, and ischemic heart disease. The control group consisted of asymptomatic patients with valvular disease.
The study’s results focused on metabolic reprogramming, microvascular dysfunction, and proinflammatory chemicals in the proper atrial tissue due to a systemic inflammatory response that may initiate and support pathological alterations in the target tissue.
Subsequent investigation revealed several putative therapeutic target molecules, including IL-1β and IL-6, whose suppression may lessen inflammation and stop the severe cardiovascular remodeling that occurs as the condition progresses.
Study director Suvi Linna-Kuosmanen, Vice Chair of the Metabolic Diseases research community at the University of Eastern Finland, said, “These findings underscore the importance of investigating all functionally relevant parts of the heart to understand the mechanisms that promote severe cardiovascular disease fully. 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.”
By analyzing the variations in gene expression in the right atrium, the research offers a glimpse into the molecular processes that underlie the main cardiovascular illnesses. These findings could lead to the development of novel treatments and preventative measures for heart failure, arrhythmias, and sudden mortality.
Journal Reference:
- Linna-Kuosmanen et al. Transcriptomic and spatial dissection of human ex vivo proper atrial tissue reveals proinflammatory microvascular changes in ischemic heart disease. Cell Reports Medicine 5, 101556, May 21, 2024. DOI: 10.1016/j.xcrm.2024.101556