Researchers have discovered significant changes occurring at the cellular level associated with coronary microvascular dysfunction (CMD), leveraging advanced bioinformatics analysis through single-cell RNA sequencing. CMD is increasingly recognized as one of the underlying causes of ischemic heart disease, affecting numerous patients who display symptoms of angina but do not have traditional blockages detected via coronary angiography.
Until now, the pathogenesis of CMD had remained somewhat obscure, largely due to the limitations of existing diagnostic tools. Recent developments underline the pressing need for effective diagnostics and therapeutic strategies to address this pressing health concern, known to impact nearly 70% of patients with coronary issues.
The recent study, proposed and executed by research teams from Shanxi Medical University and Shanxi Bethune Hospital, entailed creating rat models of CMD through controlled diet and pharmacological induction. Heart tissues from these models underwent single-cell RNA sequencing, generating a comprehensive expression profile across nearly 55,000 cells.
A staggering 28 distinct cell clusters were identified, with researchers observing marked changes: the proportion of endothelial cells—a key component of the vascular system—significantly decreased, whereas the numbers of immune and fibroblast cells rose. “These findings may provide novel potential therapeutic targets for the treatment of Coronary microvascular dysfunction,” noted the research team.
This comprehensive sequencing approach facilitated insights not previously attainable with bulk RNA sequencing methods, allowing for detailed examination of individual endothelial cell subtypes. Notably, differences were observed among various endothelial cell phenotypes, categorized as normal, mesenchymal, proliferative, and lymphatic. This classification is pivotal because dysfunctional endothelial cells contribute to the progression of CMD, and their transformation may invoke additional adverse responses within the heart tissue.
Analysis revealed the endothelial-to-mesenchymal transition (EndoMT) phenomena driving the changes among endothelial cells involved with CMD. This process engenders endothelial cells to lose their innate characteristics and adopt more aggressive attributes akin to mesenchymal cells, fostering inflammatory responses and oxidative stress—two factors known to exacerbate CMD.
The study concludes with optimism for future therapeutic interventions targeted at these cellular alterations. It posits, “By employing methods to modulate inflammation and prevent vascular remodeling, we can effectively alleviate endothelial dysfunction, aiding in the identification of therapeutic targets for CMD.” Further explorations are warranted to solidify these findings and potentially translate them to human treatments, enhancing patient outcomes, and establishing reliable biomarkers to detect CMD earlier.