Cyclic strain and motion control produce opposite oxidative responses in two human endothelial cell types

Abstract

Sung H-J, Yee A, Eskin SG, McIntire LV. Cyclic strain and motion control produce opposite oxidative responses in two human endothelial cell types. Am J Physiol Cell Physiol 293: C87-C94, 2007. First published February 21, 2007 doi:10.1152/ajpcell.00585.2006.-The phenotype of endothelial cells (ECs) is specific to the vascular bed from which they originate. To examine how mechanical forces alter the phenotype of different ECs, we compared the effects of cyclic strain and motion control on reactive oxygen species (ROS) production and metabolism and cell adhesion molecule expression in human umbilical vein endothelial cells (HUVEC) vs. human aortic endothelial cells (HAEC). HUVEC and HAEC were subjected to cyclic strain (10% or 20%, 1 Hz), to a motion control that simulated fluid agitation over the cells without strain, or to static conditions for 24 h. We measured H2O2 production with dichlorodihydrofluorescein acetate and superoxide with dihydroethidium fluorescence changes; superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) activities spectrophotometrically; and vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 protein expression with Western blot analyses. HUVEC under cyclic strain showed 1) higher intracellular H2O2 levels, 2) increased SOD, catalase, and GPx activities, and 3) greater VCAM-1 and ICAM-1 protein expression, compared with motion control or static conditions. However, in HAEC, motion control induced higher levels of ROS, enzyme activities associated with ROS defense, and VCAM-1 and ICAM-1 expression than cyclic strain. The opposite responses obtained with these two human EC types may reflect their vessels of origin, in that HAEC are subjected to higher cyclic strain deformations in vivo than HUVEC.

Upregulation of Glutathione Peroxidase Offsets Stretch-Induced Proatherogenic Gene Expression in Human Endothelial Cells

“…Thus, besides the documented stretch-induced rise in GSH peroxidase activity in human cultured endothelial cells, 49 the present findings demonstrate for the first time by using an antisense ODN approach the pivotal role of GPx-1 expression in the protection against oxidative stress and a dedifferentiation of these cells toward a proinflammatory phenotype both under static conditions and in response to cyclic stretch. They further reveal that this biomechanical force upregulates GPx-1 expression in human cultured endothelial cells through the generation of ROS, more precisely H 2 O 2 , 51 followed by activation of the transcription factor C/EBP via the p38 MAPK pathway.…”

“…47 In human umbilical vein endothelial cells (passages 3 to 8) shear stress causes a decrease in both GSH peroxidase and catalase activity, 48 whereas exposure of the same cells (passages 4 to 6) to cyclic stretch not only raises the level of H 2 O 2 but (consequently) also the activity of GSH peroxidase. 49 In our primary human umbilical vein endothelial cells exposure to shear stress (30 dyn/cm 2 , 12 hours exposure) caused a moderate (23% to 35%) decrease in GPx-1 expression both on the mRNA and protein level. The reason for these somewhat discrepant findings between bovine and human endothelial cells is unclear at present but may not simply be related to a species difference.…”

Increased Vascular Cell Adhesion Molecule–1 Was Associated with Impaired Endothelium–Dependent Relaxation of Cerebral and Carotid Arteries in Simulated Microgravity Rats

“…VCAM-1 is also referred to inducible cell adhesion molecule CD106 with a molecule weight of 100-110 kDa. Increased cyclic strain [9] and oscillatory flow [10] upregulate the expression of VCAM-1, which is mediated by a variety of inflammatory signals through the NK-κB pathway [7,11], and it mediates lymphocyte adherence via interaction with very late antigen-4 [12,13]. The lymphocytes release cytokines such as IL-1β, TNF-α, and IL-6 which are believed to result in vascular remodeling [14] and higher vascular reactivity [15].…”

Pro-angiogenic and Anti-inflammatory Regulation by Functional Peptides Loaded in Polymeric Implants for Soft Tissue Regeneration

“…36 Human bloodderived monocytes were purchased from Advanced Biotechnologies and differentiated into monocyte-derived macrophages (MDMs) by seeding at a density of 2 · 10 7 cells/ 10 mL DMEM (Invitrogen) with 20% fetal calf serum (Intergen), 10% human serum (Nabi), and 5 ng/mL macrophage colony-stimulating factor (Sigma) for 9 days. 37 HUVECs and MDMs were used because they are well-studied models of angiogenesis and inflammation in the tissue remodeling phase, respectively.…”

“…37 HUVECs and MDMs were used because they are well-studied models of angiogenesis and inflammation in the tissue remodeling phase, respectively. 36,37 Porous scaffolds with 8% crosslinking were punched into 24-well size discs, sterilized under UV for 1 h per side, and filled with the collagen gel either with or without peptides.…”