Chlorogenic acid enhances endothelial barrier function and promotes endothelial tube formation: A proteomics approach and functional validation
Issued Date
2022-09-01
Resource Type
ISSN
07533322
eISSN
19506007
Scopus ID
2-s2.0-85135503531
Pubmed ID
36076497
Journal Title
Biomedicine and Pharmacotherapy
Volume
153
Rights Holder(s)
SCOPUS
Bibliographic Citation
Biomedicine and Pharmacotherapy Vol.153 (2022)
Suggested Citation
Wuttimongkolchai N., Kanlaya R., Nanthawuttiphan S., Subkod C., Thongboonkerd V. Chlorogenic acid enhances endothelial barrier function and promotes endothelial tube formation: A proteomics approach and functional validation. Biomedicine and Pharmacotherapy Vol.153 (2022). doi:10.1016/j.biopha.2022.113471 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/86838
Title
Chlorogenic acid enhances endothelial barrier function and promotes endothelial tube formation: A proteomics approach and functional validation
Author's Affiliation
Other Contributor(s)
Abstract
Chlorogenic acid (CGA) is a highly abundant bioactive compound in green coffee beans. CGA has protective roles in various cardiovascular diseases, suggesting that it may affect endothelial cells lining the blood vessels. However, cellular mechanisms underlying its beneficial effects remained unclear. We therefore performed quantitative proteomics of CGA-treated human endothelial cells, followed by enrichment/pathway analyses, and functional validation using various assays. EA.hy926 cells were treated with 5 µM CGA for 24-h before nanoLC-LTQ-Orbitrap MS/MS analyses. Comparing with control cells, the CGA-treated cells had 185 differentially expressed proteins. Of these, up-regulations of podocalyxin-1 and lamin A/C were confirmed by immunoblotting. Enrichment analysis revealed that CGA mainly affected RNA-binding proteins involved in protein targeting to membrane and exosomal secretion. KEGG pathway analysis of proteins in RNA metabolic process/gene expression cluster revealed the involvement of Rap1 signaling, PI3K/AKT signaling and spliceosome, suggesting their potential roles in modulating tight junction (TJ) barrier and angiogenesis. Functional validation revealed significant increases in ZO-1 (a TJ-associated protein) expression and transendothelial electrical resistance (TEER) in the CGA-treated cells. Finally, CGA enhanced capillary-like endothelial tube formation and secretion of angiopoietin-2 (an angiogenic factor). These novel findings provide insights into cellular mechanisms underlying the beneficial effects of CGA on cardiovascular system via enhancement of endothelial TJ barrier function and angiogenesis.