Cytoskeletal structure regulates endothelial cell immunogenicity independent of fluid shear stress

Keri B. Vartanian, Michelle A. Berny, Owen McCarty, Stephen R. Hanson, Monica Hinds

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The cardiovascular disease atherosclerosis is directly linked to the functions of endothelial cells (ECs), which are affected by fluid shear stress (FSS). High, unidirectional FSS causes EC elongation with aligned cytoskeletal components and nonimmunogenic EC functions that protect against atherosclerosis. In contrast, low, oscillatory FSS is associated with cobblestone-shaped ECs with randomly oriented cytoskeletons and proinflammatory EC functions that promote atherosclerosis. Whether EC shape plays a role in EC immunogenic functions, independent of FSS, has not been previously determined. The goal of this study was to determine the effect of EC elongation and cytoskeletal alignment on the expression of inflammatory genes and functions. With the use of micropatterned lanes, EC elongation and cytoskeletal alignment were achieved in the absence of FSS. EC gene expression of key inflammation markers determined that the elongation and cytoskeletal alignment of micropattern-elongated ECs (MPECs) alone signifi-cantly downregulated VCAM-1 while having no effect on E-selectin and ICAM-1. The positive control of FSS-elongated ECs promoted E-selectin and VCAM-1 downregulation and upregulation of ICAM-1. Functionally, monocytic U937 cells formed weaker interactions on the surface of MPECs compared with cobblestone ECs. Interestingly, MPEC expression of the known FSS-dependent transcription factor krüppel-like factor 2 (KLF2), which promotes a nonimmunogenic EC phenotype, was significantly upregulated in MPECs compared with cobblestone ECs. Cytoskeletal regulation of KLF2 expression was shown to be dependent on microtubules. Therefore, the cellular elongation and cytoskeletal alignment of MPECs regulated immunogenic gene expression and functions and may act synergistically with FSS to create an EC surface with reduced inflammatory capability.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume298
Issue number2
DOIs
StatePublished - Feb 2010

Fingerprint

Endothelial Cells
Atherosclerosis
E-Selectin
Vascular Cell Adhesion Molecule-1
Intercellular Adhesion Molecule-1
Gene Expression
Down-Regulation
U937 Cells
Cell Shape
Cytoskeleton
Microtubules
Transcription Factors
Cardiovascular Diseases
Up-Regulation
Inflammation
Phenotype

Keywords

  • Inflammation
  • Krüppel-like factor 2
  • Micropattern
  • Vascular cell adhesion molecule-1

ASJC Scopus subject areas

  • Cell Biology
  • Physiology
  • Medicine(all)

Cite this

Cytoskeletal structure regulates endothelial cell immunogenicity independent of fluid shear stress. / Vartanian, Keri B.; Berny, Michelle A.; McCarty, Owen; Hanson, Stephen R.; Hinds, Monica.

In: American Journal of Physiology - Cell Physiology, Vol. 298, No. 2, 02.2010.

Research output: Contribution to journalArticle

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