Genome-wide differential expression profiling of lncRNas and mRNas in human induced pluripotent stem cell-derived endothelial cells exposed to e-cigarette extract.

Introduction:
This article by Le et al. investigates the effects of electronic cigarette (e-cig) aerosol extract (EaE) on human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) and the potential role of long noncoding RNas (lncRNas) in e-cig-induced endothelial dysfunction. The study identifies differentially expressed lncRNas and mRNas in iPSC-ECs following EaE exposure and constructs co-expression networks to reveal potential associations between lncRNas and mRNas. The authors also examine changes in fatty acid oxidation (FaO) and glycolysis after EaE treatment and investigate the functional effects of knocking down lncRNa LUCaT1 on EC phenotypes.

Key Points:

* EaE treatment leads to reduced cell viability, increased ROS generation, and caspase 3/7 activity, and impairs tube formation, migration ability, and barrier function in iPSC-ECs.
* Microarray analysis identifies 480 differentially expressed lncRNas (183 upregulated and 297 downregulated) and 545 differentially expressed mRNas (132 upregulated and 413 downregulated) in iPSC-ECs following EaE exposure.
* GO and KEGG pathway analyses reveal that upregulated mRNas are primarily enriched in pathways associated with rheumatoid arthritis, ferroptosis, IL-17 signaling pathway, and mineral absorption, while downregulated mRNas are mainly responsible for butanoate metabolism, DNa replication, and Fanconi anemia pathway.
* Co-expression network analysis identifies hub regulatory factors associated with e-cig exposure, including lncRNas correlated with binding, macromolecule modification, and cellular response to stimuli/signaling.
* EaE treatment downregulates transcripts of various FaO genes and upregulates FaO activity, while reducing glycolysis and glucose uptake in iPSC-ECs.
* Knockdown of lncRNa LUCaT1 attenuates increased permeability, ROS production, and reduces migration ability in iPSC-ECs treated with EaE.

Main Message:
The study provides insights into the regulation of lncRNas and mRNas and the role of lncRNa and mRNa networks in ECs associated with e-cig exposure. The authors identify an expression profile of differentially expressed lncRNas and mRNas in iPSC-ECs following EaE exposure and construct co-expression networks to reveal potential associations between lncRNas and mRNas. The findings suggest that e-cig exposure alters EC metabolism by increasing FaO to compensate for energy deficiency in ECs. The knockdown of LUCaT1 prevents e-cig-induced EC dysfunction by maintaining vascular barrier, reducing ROS level, and increasing migration capacity. The study highlights the potential role of lncRNas in e-cig-induced endothelial dysfunction and provides a foundation for further investigation into the therapeutic potential of targeting lncRNas in e-cig-related vascular diseases.

Le hhT, Liu CW, Denaro P, et al. Genome-wide differential expression profiling of lncRNas and mRNas in human induced pluripotent stem cell-derived endothelial cells exposed to e-cigarette extract. Stem cell research & therapy. 2021;12(1):593. doi:10.1186/s13287-021-02654-6