Cyclic strain induces an oxidative stress in endothelial cells.
Howard, Adam B., R. Wayne Alexander, Robert M. Nerem, Kathy K.
Griendling, and W. Robert Taylor.
Division of Cardiology, Emory University, Atlanta, GA 30322,
Veterans Affairs Medical Center, Decatur, GA 30033, Bioengineering
Center and School of Mechanical Engineering, Georgia Institute of
Technology, Atlanta, GA 30332
APStracts 3:0276C, 1996.
Hypertension imposes an oxidant stress upon the aorta and also causes
mechanical deformation of the aortic wall. To assess whether
deformation causes an oxidative stress, isolated porcine aortic
endothelial cells (PAECs) were subjected to cyclic strain, and the
cumulative amount of thiobarbituric acid reactive substances (TBARS,
an index of lipid peroxidation) and H2O2 (a reactive oxygen species)
was measured in the eluent at 2, 6, and 24 hours. TBARS was increased
by 40.5 9.2% after 24 hours between cells exposed to cyclic strain
and static controls (p<0.05). No difference was seen at 2 and 6
hours. H2O2 release was increased after 6 and 24 hours of cyclic
strain by 22.0 8.0 and 57.6 11.1 nmol H2O2/mg respectively
(p<0.005), but not increased after 2 hours of strain. In
vascular smooth muscle cells, TBARS were not observed and H2O2
release was not increased by cyclic strain. To investigate a
potential source of H2O2 induced by strain, the activity of
NADH/NADPH oxidase, a superoxide-generating enzyme, was measured by
chemiluminescence. After 2 hours, cells exposed to cyclic strain had
greater activity than static controls (531.0 68.4 vs. 448.3 54.2 pmol
O2-/mg/sec respectively when incubated with NADH, p<0.005; 85.8
8.9 vs. 71.6 3.8 pmol O2-/mg/sec when incubated with NADPH,
p<0.05). No effect upon NADH/NADPH oxidase activity was seen
after 6 or 24 hours. CONCLUSIONS: 1. Cyclic strain induces an oxidant
stress in PAEC monolayers as measured by TBARS formation and H2O2
release. 2. NADH/NADPH oxidase is a potential source of H2O2 release
in cyclically strained cells. 3. Mechanical deformation of
endothelial cells may play a critical role in the generation of
oxidative stress within the vessel wall.
Received 14 March 1996; accepted in final form 27 August 1996.
APS Manuscript Number C147-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996