Disturbed flow and cyclic strain upregulate the expression of ICAM-1 and VCAM-1 in cultured human vascular endothelial cells

P. I. Lelkes, K. Kanda, C. Kettlun, T. G. Hayman, D. M. Wankowski

Research output: Contribution to journalArticlepeer-review

Abstract

One of the early warning signs of incipient vascular damage is the up-regulation of cell adhesion molecules (CAMs) on the endothelial cell (EC)lining of "high risk areas" for atherosclerotic plaque formation. It has been hypothesized that aberrant hemodynamic forces, such as non-laminar pulsatile shear stress and cyclic strain, might predispose EC to vascular lesion by locally up-regulating the expression of EC adhesion molecules (CAMs), such as ICAM-1 and VCAM-1. Previous studies have shown that high-shear laminar flow induces ICAM-1 expression while suppressing, the expression of VCAM-1. In this study, cultured human aortic and umbilical vein-derived EC were exposed for 5 h to low-shear (< 0.8 dynes/cm2) disturbed flow (DF) or to cyclic strain (CS, 1 Hz, 10% average strain). Expression of CAM at the protein level was assessed by a whole cell-based ELISA, steady-state mRNA levels were quantitated by competitive RT-PCR, Both CS and DF caused a significant (2 - 8 fold) increase in the basal expression of VCAM-1 and also, albeit to a lesser extent, in the expression of ICAM-1. Preincuabtion of the cells with 50 μM PDTC, an oxygen radical scavenger and antagonist of the activation of the nuclear transcription factor NF-kappa B abrogated both CS and DF-induced VCAM-1 expression, but not that of ICAM-1. These results suggest that complex hemodynamic forces might predispose EC to atherosclerotic lesions by facilitating the recruitment of leukocytes. Moreover, our data suggest disparate signaling mechanisms might be involved in the upregulation of the expression of ICAM-1 and VCAM-1 by aberrant hemodynamic forces.

Original languageEnglish
Pages (from-to)A224
JournalFASEB Journal
Volume11
Issue number3
StatePublished - 1997
Externally publishedYes

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