| Title | Cytoskeletal Structure Regulates Endothelial Cell Immunogenicity Independent of Fluid Shear Stress. | | Author(s) | Vartanian KB, Berny MA, McCarty OJ, Hanson SR, Hinds MT | | Institution | 1Oregon Health & Science University. | | Source | Am J Physiol Cell Physiol 2009 Nov 18. | | Abstract | The cardiovascular disease atherosclerosis is directly linked to the functions of the endothelial cells (ECs), which are affected by fluid shear stress (FSS). High, unidirectional FSS causes EC elongation with aligned cytoskeletal components and non-immunogenic EC functions protecting against atherosclerosis. In contrast, low, oscillatory FSS is associated with cobblestone-shaped ECs with a randomly oriented cytoskeleton and pro-inflammatory 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. Using micropatterned lanes EC elongation and cytoskeletal alignment were achieved in the absence of FSS. EC gene expression of the key inflammation markers determined that the elongation and cytoskeletal alignment of micropattern-elongated ECs (MPEC) alone significantly 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 to cobblestone ECs. Interestingly, MPEC expression of the known FSS-dependent transcription factor krüppel-like factor 2 (KLF2), which promotes non-immunogenic EC phenotype, was significantly upregulated in MPECs compared to 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19923423 |
|
