Pericardial Fluid–Derived Small Extracellular Vesicles from Patients with Coronary Disease Alter the Lipidome of Human Coronary Artery Endothelium

Abstract

Background

To date, we have lacked an understanding of how factors in the pericardial fluid (PF) of patients with coronary artery disease (CAD) can influence the lipidome of coronary artery endothelium. This study explores the impact of PF-derived extracellular vesicles (EVs) on the lipidome of human coronary artery endothelial cells (HCAECs) in patients with CAD.

Methods

In this observational study, PF was collected from patients with CAD (n = 3) and without CAD (n = 3). PF-derived small EVs were isolated and characterized using microfluidic resistive pulse sensing. HCAECs were exposed to these EVs, and untargeted liquid chromatography-mass spectrometry was subsequently used to determine the lipidome of the HCAECs. In silico analysis was used to evaluate changes in lipid species and classes.

Results

A total of 1043 lipid species were identified in untreated HCAECs and HCAECs treated with PF-derived small EVs. The predominant lipid types were glycerophospholipids, glycerolipids, and sphingolipids. Quantification of individual lipid classes showed HCAECs treated with PF EVs showed reduced summed intensities of lysophosphatidylglycerols and diacylglycerophosphoinositols compared to untreated controls. Treatment with PF EVs derived from Non-CAD patients led to an increase in sphingoid bases, whereas this effect was not observed with CAD-derived PF EVs. Both Non-CAD and CAD PF EV treatments resulted in elevated prenol lipids compared to controls.

Conclusions

We identify that small EVs isolated from the PF of patients with CAD alter the lipid profile and metabolism of human coronary artery endothelium. Future studies should determine whether such changes can contribute to the pathophysiology of ischemic heart disease.