Loss of fatty acid binding protein 3 ameliorates lipopolysaccharide-induced inflammation and endothelial dysfunction.

Abstract

Circulating fatty acid-binding protein 3 (FABP3) is an effective biomarker of myocardial injury and peripheral artery disease (PAD). The endothelium, which forms the inner most layer of every blood vessel, is exposed to higher levels of FABP3 in PAD or following myocardial injury, but the pathophysiological role of endothelial FABP3, the effect of FABP3 exposure on endothelial cells, and related mechanisms are unknown. Here, we aimed to evaluate the pathophysiological role of endothelial FABP3 and related mechanisms in vitro. Our molecular and functional in vitro analyses show that (1) FABP3 is basally expressed in endothelial cells; (2) inflammatory stress in the form of lipopolysaccharide (LPS) upregulated endothelial FABP3 expression; (3) loss of endogenous FABP3 protected endothelial cells against LPS-induced endothelial dysfunction; however, exogenous FABP3 exposure exacerbated LPS-induced inflammation; (4) loss of endogenous FABP3 protected against LPS-induced endothelial dysfunction by promoting cell survival and anti-inflammatory and pro-angiogenic signaling pathways. Together, these findings suggest that gain-of endothelial FABP3 exacerbates, whereas loss-of endothelial FABP3 inhibits LPS-induced endothelial dysfunction by promoting cell survival and anti-inflammatory and pro-angiogenic signaling. We propose that an increased circulating FABP3 in myocardial injury or PAD patients may be detrimental to endothelial function, and therefore, therapies aimed at inhibiting FABP3 may improve endothelial function in diseased states.

• Authors: Hien C Nguyen, Shuhan Bu, Sepideh Nikfarjam, Berk Rasheed, David C R Michels, Aman Singh, Shweta Singh, Caroline Marszal, John J McGuire, Qingping Feng, Jefferson C Frisbee, Mohammad Qadura, Krishna K Singh
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 299 Issue 3 Pg. 102921 (03 2023) ISSN: 1083-351X [Electronic] United States
• PMID: 36681124 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Fatty Acid Binding Protein 3
• Lipopolysaccharides

Topics

• Humans
• Endothelial Cells (pathology)
• Fatty Acid Binding Protein 3 (genetics)
• Inflammation (chemically induced)
• Lipopolysaccharides
• Signal Transduction (genetics)
• Cell Survival (genetics)