Adaptive response of vascular endothelial cells to an acute increase in shear stress magnitude

The adaptation of vascular endothelial cells to shear stress alteration induced by global hemodynamic changes, such as those accompanying exercise or digestion, is an essential component of normal endothelial physiology in vivo. An understanding of the transient regulation of endothelial phenotype during adaptation to changes in mural shear will advance our understanding of endothelial biology and may yield new insights into the mechanism of atherogenesis. In this study, we characterized the adaptive response of arterial endothelial cells to an acute increase in shear stress magnitude in well-defined in vitro settings. Porcine endothelial cells were preconditioned by a basal level shear stress of 15 ± 15 dyn/cm2 at 1 Hz for 24 h, after which an acute increase in shear stress to 30 ± 15 dyn/cm2 was applied. Endothelial permeability nearly doubled after 40-min exposure to the elevated shear stress and then decreased gradually. Transcriptomics studies using microarray techniques identified 86 genes that were sensitive to the elevated shear. The acute increase in shear stress promoted the expression of a group of anti-inflammatory and antioxidative genes. The adaptive response of the global gene expression profile is triphasic, consisting of an induction period, an early adaptive response (ca. 45 min) and a late remodeling response. Our results suggest that endothelial cells exhibit a specific phenotype during the adaptive response to changes in shear stress; this phenotype is different than that of fully adapted endothelial cells.

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Adaptive response of vascular endothelial cells to an acute increase in shear stress frequency

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00174.2013 ◽

2013 ◽

Vol 305 (6) ◽

pp. H894-H902 ◽

Cited By ~ 13

Author(s):

Ji Zhang ◽

Morton H. Friedman

Keyword(s):

Endothelial Cells ◽

Shear Stress ◽

Adaptive Response ◽

Vascular Endothelial Cells ◽

Endothelial Permeability ◽

Blood Flow Rate ◽

Beneficial Effects ◽

Acute Increase ◽

Local Shear ◽

Cycle Regulation

Local shear stress sensed by arterial endothelial cells is occasionally altered by changes in global hemodynamic parameters, e.g., heart rate and blood flow rate, as a result of normal physiological events, such as exercise. In a recently study ( 41 ), we demonstrated that during the adaptive response to increased shear magnitude, porcine endothelial cells exhibited an unique phenotype featuring a transient increase in permeability and the upregulation of a set of anti-inflammatory and antioxidative genes. In the present study, we characterize the adaptive response of these cells to an increase in shear frequency, another important hemodynamic parameter with implications in atherogenesis. Endothelial cells were preconditioned by a basal-level sinusoidal shear stress of 15 ± 15 dyn/cm2 at 1 Hz, and the frequency was then elevated to 2 Hz. Endothelial permeability increased slowly after the frequency step-up, but the increase was relatively small. Using microarrays, we identified 37 genes that are sensitive to the frequency step-up. The acute increase in shear frequency upregulates a set of cell-cycle regulation and angiogenesis-related genes. The overall adaptive response to the increased frequency is distinctly different from that to a magnitude step-up. However, consistent with the previous study, our data support the notion that endothelial function during an adaptive response is different than that of fully adapted endothelial cells. Our studies may also provide insights into the beneficial effects of exercise on vascular health: transient increases in frequency may facilitate endothelial repair, whereas similar increases in shear magnitude may keep excessive inflammation and oxidative stress at bay.

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The Adaptive Response of Endothelial Transcription to Increased Shear Stress In Vitro

ASME 2010 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2010-19318 ◽

2010 ◽

Author(s):

Ji Zhang ◽

Morton H. Friedman

Keyword(s):

Endothelial Cells ◽

Shear Stress ◽

Adaptive Response ◽

Inflammatory Responses ◽

Vascular Endothelial Cells ◽

Morphological Changes ◽

Substantial Effect ◽

Endothelial Phenotype

Previous studies have shown a substantial effect of shear stress on endothelial phenotype and functions such as production of nitric oxide, secretion of growth factors, inflammatory responses, production of reactive oxygen species, permeability to macromolecules and cytoskeletal remodeling [1–3]. However, the dynamics of the endothelial adaptive response to changes in shear stress are largely unknown. The response of vascular endothelial cells to alterations in shear stress is an essential component of normal endothelial physiology, since local shear stress can be altered in vivo by the global hemodynamic changes that are caused by daily activities such as exercise, sleep, smoking and stress. The duration of these changes ranges from minutes to hours. When adapting to the altered shear stress, endothelial cells undergo a series of structural remodeling and morphological changes, and a transient alteration of endothelial phenotype will be induced. An understanding of the transient regulation of endothelial phenotype will not only improve our knowledge of normal endothelial physiology but also yield insights into mechanisms underlying atherogenesis.

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Synthesis and physiological activity of heterodimers comprising different splice forms of vascular endothelial growth factor and placenta growth factor

Biochemical Journal ◽

10.1042/bj3160703 ◽

1996 ◽

Vol 316 (3) ◽

pp. 703-707 ◽

Cited By ~ 34

Author(s):

Ralf BIRKENHÄGER ◽

Bernard SCHNEPPE ◽

Wolfgang RÖCKL ◽

Jörg WILTING ◽

Herbert A. WEICH ◽

...

Keyword(s):

Endothelial Cells ◽

Growth Factor ◽

Vascular Endothelial Cells ◽

Physiological Activity ◽

Expression System ◽

Vascular Endothelial ◽

Placenta Growth Factor ◽

Splice Forms

Vascular endothilial growth factor (VEGF) and placenta growth factor (PIGF) are members of a dimeric-growth-factor family with angiogenic properties. VEGF is a highly potent and specific mitogen for endothelial cells, playing a vital role in angiogenesis in vivo. The role of PIGF is less clear. We expressed the monomeric splice forms VEGF-165, VEGF-121, PIGF-1 and PlGF-2 as unfused genes in Escherichia coli using the pCYTEXP expression system. In vitro dimerization experiments revealed that both homo- and hetero-dimers can be formed from these monomeric proteins. The dimers were tested for their ability to promote capillary growth in vivo and stimulate DNA synthesis in cultured human vascular endothelial cells. Heterodimers comprising different VEGF splice forms, or combinations of VEGF/PlGF splice forms, showed mitogenic activity. The results demonstrate that four different heterodimeric growth factors are likely to have as yet uncharacterized functions in vivo.

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Interaction between vascular endothelial cells and vascular intimal spindle-shaped cells in vitro

Journal of Cell Science ◽

10.1242/jcs.60.1.89 ◽

1983 ◽

Vol 60 (1) ◽

pp. 89-102

Author(s):

D de Bono ◽

C. Green

Keyword(s):

Extracellular Matrix ◽

Endothelial Cells ◽

Vascular Endothelial Cells ◽

Three Dimensional ◽

Vascular Endothelial ◽

Pure Cultures ◽

Species Specific ◽

Endothelial Growth Factor

The interactions between human or bovine vascular endothelial cells and fibroblast-like vascular intimal spindle-shaped cells have been studied in vitro, using species-specific antibodies to identify the different components in mixed cultures. Pure cultures of endothelial cells grow as uniform, nonoverlapping monolayers, but this growth pattern is lost after the addition of spindle cells, probably because the extracellular matrix secreted by the latter causes the endothelial cells to modify the way they are attached to the substrate. The result is a network of tubular aggregates of endothelial cells in a three-dimensional ‘polylayer’ of spindle-shaped cells. On the other hand, endothelial cells added to growth-inhibited cultures of spindle-shaped cells will grow in sheets over the surface of the culture. Human endothelial cells grown in contact with spindle-shaped cells have a reduced requirement for a brain-derived endothelial growth factor. The interactions of endothelial cells and other connective tissue cells in vitro may be relevant to the mechanisms of endothelial growth and blood vessel formation in vivo, and emphasize the potential importance of extracellular matrix in controlling endothelial cell behaviour.

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CYLD regulates angiogenesis by mediating vascular endothelial cell migration

Blood ◽

10.1182/blood-2009-10-248526 ◽

2010 ◽

Vol 115 (20) ◽

pp. 4130-4137 ◽

Cited By ~ 52

Author(s):

Jinmin Gao ◽

Lei Sun ◽

Lihong Huo ◽

Min Liu ◽

Dengwen Li ◽

...

Keyword(s):

Endothelial Cells ◽

Cell Migration ◽

Endothelial Cell ◽

Vascular Endothelial Cells ◽

Vascular Endothelial Cell ◽

Tube Formation ◽

Endothelial Cell Migration ◽

Vascular Endothelial

Cylindromatosis (CYLD) is a deubiquitinase that was initially identified as a tumor suppressor and has recently been implicated in diverse normal physiologic processes. In this study, we have investigated the involvement of CYLD in angiogenesis, the formation of new blood vessels from preexisting ones. We find that knockdown of CYLD expression significantly impairs angiogenesis in vitro in both matrigel-based tube formation assay and collagen-based 3-dimensional capillary sprouting assay. Disruption of CYLD also remarkably inhibits angiogenic response in vivo, as evidenced by diminished blood vessel growth into the angioreactors implanted in mice. Mechanistic studies show that CYLD regulates angiogenesis by mediating the spreading and migration of vascular endothelial cells. Silencing of CYLD dramatically decreases microtubule dynamics in endothelial cells and inhibits endothelial cell migration by blocking the polarization process. Furthermore, we identify Rac1 activation as an important factor contributing to the action of CYLD in regulating endothelial cell migration and angiogenesis. Our findings thus uncover a previously unrecognized role for CYLD in the angiogenic process and provide a novel mechanism for Rac1 activation during endothelial cell migration and angiogenesis.

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Different Effects of Orbital Shear Stress on Vascular Endothelial Cells: Comparison with the Results of In Vivo Study with Rats

Vascular Specialist International ◽

10.5758/vsi.2015.31.2.33 ◽

2015 ◽

Vol 31 (2) ◽

pp. 33-40 ◽

Cited By ~ 5

Author(s):

Hyosoo Kim ◽

Keun Ho Yang ◽

Hyunjin Cho ◽

Geumhee Gwak ◽

Sun Cheol Park ◽

...

Keyword(s):

Endothelial Cells ◽

Shear Stress ◽

Vascular Endothelial Cells ◽

In Vivo Study ◽

Vascular Endothelial

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Origin and diversity of embryonic endothelium/endocardium

10.1093/med/9780198757269.003.0005 ◽

2018 ◽

Author(s):

LeShana SaintJean ◽

H.S. Baldwin

Keyword(s):

Endothelial Cells ◽

Heart Development ◽

Vascular Endothelial Cells ◽

Coronary Vessels ◽

Cell Types ◽

Genetic Profile ◽

Vascular Endothelial ◽

Tremendous Progress

The endocardium represents a distinct population of endothelial cells that arises during the initiation of heart development. Endocardial cells can easily be distinguished from most of the other cardiac cell types. However, endocardial and vascular endothelial cells contain a similar genetic profile that limits the ability to study each group independently. Despite these limitations, tremendous progress has been made in identifying the different roles of endocardial cells throughout heart development. Initial studies focused on the origin of endocardial cells and their role in valvulogenesis, trabeculation, and formation of the ventricular and atrial septum. With the advancement of microscopy and the availability of endocardial specific reporter models (in vitro and in vivo) we have obtained more insight into the molecular, structural, and functional complexity of the endocardium. Additional studies have demonstrated how the endocardium is also involved in the development of coronary vessels within the compact myocardium and in heart regeneration.

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