Novel Knowledge-Based Transcriptomic Profiling of Lipid Lysophosphatidylinositol-Induced Endothelial Cell Activation

Area of Science:

• Endothelial Cell Biology
• Lipid Signaling
• Transcriptomics

Background:

• Pro-inflammatory lysophosphatidylinositols (LPIs) are implicated in cardiovascular health.
• Human aortic endothelial cells (HAECs) play a crucial role in vascular inflammation.
• The specific mechanisms by which LPIs affect HAEC activation are not fully understood.

Purpose of the Study:

• To investigate whether LPIs upregulate adhesion/signaling and secretory proteins in HAEC activation.
• To develop a knowledge-based transcriptomic formula for profiling RNA-Seq data in endothelial cells.
• To identify novel therapeutic targets for LPI-mediated diseases.

Main Methods:

• Development of an EC biology knowledge-based transcriptomic formula.
• Profiling of RNA-Seq data from human aortic endothelial cells (HAECs).
• Analysis of gene expression changes, including clusters of differentiation (CDs), secretomic genes (SGs), transcription factors (TFs), mitochondrial genes (mitoCarta), and reactive oxygen species (ROS) regulators.
• Utilized Cytoscape software for integrated pathway analysis.

Main Results:

• G protein-coupled receptor 55 (GPR55), the LPI receptor, is expressed in the endothelium and upregulated in hyperlipidemia.
• LPIs significantly upregulate 43 clusters of differentiation (CDs) in HAECs, promoting activation, immune trans-differentiation, and inflammatory responses.
• LPIs induce the expression of 640 secretomic genes, including canonical SGs, caspase-related SGs, exosome SGs, cytokines, and chemokines.
• LPIs upregulate 172 transcription factors (TFs), 152 mitochondrial genes, and 18 ROS regulators, orchestrating transcriptomic remodeling.
• Integrated analysis revealed that LPI-upregulated TFs, mitochondrial genes, and ROS regulators synergistically promote HAEC activation.

Conclusions:

• LPIs are potent activators of human aortic endothelial cells (HAECs), driving inflammatory and immune responses.
• The study establishes a novel transcriptomic profiling strategy for endothelial cell biology.
• Findings identify LPI-regulated pathways and molecules as potential therapeutic targets for cardiovascular diseases, inflammatory conditions, and related disorders.