Bioinformatics analysis of coronary microvascular dysfunction in rats based on single-cell RNA sequencing

Area of Science:

• Cardiovascular Biology
• Molecular Cardiology
• Genomics

Background:

• Coronary microvascular dysfunction (CMD) is a key factor in ischemic heart disease, yet its pathogenesis is not fully understood.
• CMD presents a novel therapeutic avenue for coronary artery diseases.
• Inconsistent research findings necessitate further investigation into CMD's underlying mechanisms.

Purpose of the Study:

• To investigate single-cell gene expression profiles in a rat model of CMD.
• To specifically analyze endothelial cell gene expression characteristics in CMD.
• To identify potential therapeutic targets for CMD.

Main Methods:

• Establishment of a rat model for coronary microvascular dysfunction.
• Single-cell RNA sequencing of cardiac apical tissue.
• Bioinformatic analysis of 55,419 cells, identifying 28 cell clusters.

Main Results:

• Endothelial cells were significantly reduced, while fibroblasts increased in the CMD group compared to controls.
• Endothelial cells were classified into normal, mesenchymal, proliferative, and lymphatic phenotypes.
• The CMD group showed increased immune cells, inflammation, and oxidative stress.

Conclusions:

• CMD involves significant alterations in cardiac cell populations, particularly endothelial cells and fibroblasts.
• Mesenchymal and proliferative endothelial cells appear to arise from normal endothelial cells in CMD.
• Findings suggest increased inflammation and oxidative stress contribute to CMD pathogenesis, highlighting potential therapeutic targets.