On-chip endothelial inflammatory phenotyping.

J. Sherrod DeVerse, Keith A. Bailey, Greg A. Foster, Vaishali Mittal, Stuart M. Altman, Scott I. Simon, Anthony G. Passerini

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Atherogenesis is potentiated by metabolic abnormalities that contribute to a heightened state of systemic inflammation resulting in endothelial dysfunction. However, early functional changes in endothelium that signify an individual's level of risk are not directly assessed clinically to help guide therapeutic strategy. Moreover, the regulation of inflammation by local hemodynamics contributes to the non-random spatial distribution of atherosclerosis, but the mechanisms are difficult to delineate in vivo. We describe a lab-on-a-chip based approach to quantitatively assay metabolic perturbation of inflammatory events in human endothelial cells (EC) and monocytes under precise flow conditions. Standard methods of soft lithography are used to microfabricate vascular mimetic microfluidic chambers (VMMC), which are bound directly to cultured EC monolayers. These devices have the advantage of using small volumes of reagents while providing a platform for directly imaging the inflammatory events at the membrane of EC exposed to a well-defined shear field. We have successfully applied these devices to investigate cytokine-, lipid- and RAGE-induced inflammation in human aortic EC (HAEC). Here we document the use of the VMMC to assay monocytic cell (THP-1) rolling and arrest on HAEC monolayers that are conditioned under differential shear characteristics and activated by the inflammatory cytokine TNF-α. Studies such as these are providing mechanistic insight into atherosusceptibility under metabolic risk factors.

Original languageEnglish (US)
JournalJournal of visualized experiments : JoVE
Issue number65
StatePublished - 2012
Externally publishedYes

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Endothelial cells
Endothelial Cells
Microfluidics
Inflammation
Blood Vessels
Monolayers
Assays
Atherosclerosis
Cytokines
Equipment and Supplies
Lab-on-a-chip
Hemodynamics
Lithography
Lipids
Spatial distribution
Endothelium
Monocytes
Cultured Cells
Membranes
Imaging techniques

ASJC Scopus subject areas

  • Medicine(all)

Cite this

DeVerse, J. S., Bailey, K. A., Foster, G. A., Mittal, V., Altman, S. M., Simon, S. I., & Passerini, A. G. (2012). On-chip endothelial inflammatory phenotyping. Journal of visualized experiments : JoVE, (65).

On-chip endothelial inflammatory phenotyping. / DeVerse, J. Sherrod; Bailey, Keith A.; Foster, Greg A.; Mittal, Vaishali; Altman, Stuart M.; Simon, Scott I.; Passerini, Anthony G.

In: Journal of visualized experiments : JoVE, No. 65, 2012.

Research output: Contribution to journalArticle

DeVerse, JS, Bailey, KA, Foster, GA, Mittal, V, Altman, SM, Simon, SI & Passerini, AG 2012, 'On-chip endothelial inflammatory phenotyping.', Journal of visualized experiments : JoVE, no. 65.
DeVerse JS, Bailey KA, Foster GA, Mittal V, Altman SM, Simon SI et al. On-chip endothelial inflammatory phenotyping. Journal of visualized experiments : JoVE. 2012;(65).
DeVerse, J. Sherrod ; Bailey, Keith A. ; Foster, Greg A. ; Mittal, Vaishali ; Altman, Stuart M. ; Simon, Scott I. ; Passerini, Anthony G. / On-chip endothelial inflammatory phenotyping. In: Journal of visualized experiments : JoVE. 2012 ; No. 65.
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