From the Division of Hypertension and Vascular Medicine, CHUV, Lausanne,
Switzerland.
Correspondence to Dr Paolo Silacci, Division of Hypertension, Hôpital Nestlé, Ave Pierre Decker, CHUV, 1011 Lausanne, Switzerland. E-mail Paolo.Silacci{at}chuv.hospvd.ch
Abstract
Abstract—Nitric oxide (NO) has been
demonstrated to play a central role in vascular biology and
pathobiology. The expression of endothelial NO synthase
(eNOS) is regulated in part by blood flow–induced mechanical factors.
The purpose of this study was to evaluate how the expression of eNOS
mRNA correlates with the activation of its promoter in both
arterial and venous endothelial cells (ECs)
exposed to mechanical forces, ie, shear stress and cyclic
circumferential stretch. Bovine aortic ECs (BAECs) and EA hy.926, a
cell line derived from human umbilical vein ECs, were grown on the
inside of elastic tubes and subjected to combinations of pressure,
pulsatile shear stress, and cyclic circumferential stretch for 24
hours. Two patterns of shear stress were used: unidirectional (mean of
6, ranging from 3 to 9 dyne/cm2) and oscillatory (mean of
0.3, ranging from -3 to +3 dyne/cm2). The expression of
eNOS mRNA was quantified by Northern blot analysis. Activation
of the promoter was assessed by luciferase activity after the cells
were transiently transfected before the flow experiments with a plasmid
construct containing the fully functional eNOS promoter coupled to a
luciferase reporter gene. Expression of eNOS mRNA was increased and
promoter activity was enhanced by unidirectional shear stress compared
with static control. Oscillatory shear slightly upregulated eNOS mRNA
in BAECs, whereas it downregulated eNOS mRNA in EA hy.926. In both
BAECs and EA hy.926, there was a good correlation between the increase
in eNOS mRNA expression and promoter activation by unidirectional shear
stress. In contrast, in both BAECs and EA hy.926 cells exposed to shear
stress, cyclic stretch did not change eNOS mRNA expression, but the
activation of eNOS promoter was significantly lower. Moreover, when ECs
were exposed to oscillatory shear stress, there was a dramatic
activation of the eNOS promoter. These results demonstrate that
unidirectional shear stress increases eNOS mRNA expression via a
transcriptional mechanism. However, oscillatory shear stress and cyclic
stretch appear to control eNOS expression through posttranscriptional
regulatory events.
© 1998 American Heart Association, Inc.
Third Workshop on Structure and Function of Large Arteries: Part II
Nitric Oxide Synthase Expression in Endothelial Cells Exposed to Mechanical Forces
Key Words: atherosclerosis • endothelium • stress, mechanical • nitric oxide synthase • promoters
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