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ORIGINAL RESEARCH article

Front. Physiol.
Sec. Vascular Physiology
Volume 15 - 2024 | doi: 10.3389/fphys.2024.1431847
This article is part of the Research Topic Mechanotransduction in Vascular Development and Disease View all 7 articles

Flow-Mediated Modulation of the Endothelial Cell Lipidome

Provisionally accepted
Soon-Gook Hong Soon-Gook Hong John P. Kennelly John P. Kennelly Kevin J. Williams Kevin J. Williams Steven J. Bensinger Steven J. Bensinger Julia J. Mack Julia J. Mack *
  • University of California, Los Angeles, Los Angeles, California, United States

The final, formatted version of the article will be published soon.

    The luminal surface of the endothelium is exposed to dynamic blood flow patterns that are known to affect endothelial cell phenotype. While many studies have documented the phenotypic changes by gene or protein expression, less is known about the role of blood flow pattern on the endothelial cell (EC) lipidome. In this study, shotgun lipidomics was conducted on human aortic ECs (HAECs) exposed to unidirectional laminar flow (UF), disturbed flow (DF), or static conditions for 48 hrs. A total of 520 individual lipid species from 17 lipid subclasses were detected. Total lipid abundance was significantly increased for HAECs exposed to DF compared to UF conditions. Despite the increase in the total lipid abundance, HAECs maintained equivalent composition of each lipid subclass (% of total lipid) under DF and UF. However, by lipid composition (% of total subclass), 28 lipid species were significantly altered between DF and UF. Complimentary RNA sequencing of HAECs exposed to UF or DF revealed changes in transcripts involved in lipid metabolism. Shotgun lipidomics was also performed on HAECs exposed to pro-inflammatory agonists lipopolysaccharide (LPS) or Pam3CSK4 (Pam3) for 48 hrs. Exposure to LPS or Pam3 reshaped the EC lipidome in both unique and overlapping ways. In conclusion, exposure to flow alters the EC lipidome and ECs undergo stimulus-specific lipid reprogramming in response to pro-inflammatory agonist exposure. Ultimately, this work provides a resource to profile the transcriptional and lipidomic changes that occur in response to applied flow that can be accessed by the vascular biology community to further dissect and extend our understanding of endothelial lipid biology.

    Keywords: shear stress, Flow pattern, endothelial cell, lipid profile, Inflammation

    Received: 13 May 2024; Accepted: 01 Jul 2024.

    Copyright: © 2024 Hong, Kennelly, Williams, Bensinger and Mack. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Julia J. Mack, University of California, Los Angeles, Los Angeles, 90095, California, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.