scholarly journals Mechanosensing of blood flow in vascular endothelial cells

2011 ◽  
Vol 138 (5) ◽  
pp. 196-200 ◽  
Author(s):  
Kimiko Yamamoto ◽  
Joji Ando
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial

scholarly journals Disturbed flow: p53 SUMOylation in the turnover of endothelial cells

2011 ◽  
Vol 193 (5) ◽  
pp. 805-807 ◽  
Author(s):  
Wakako Takabe ◽  
Noah Alberts-Grill ◽  
Hanjoong Jo
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Protein Inhibitor ◽  
Disturbed Flow ◽  
Antiapoptotic Protein ◽  
Kinase C

Disturbed blood flow induces apoptosis of vascular endothelial cells, which causes atherosclerosis. In this issue, Heo et al. (2011. J. Cell Biol. doi:10.1083/jcb.201010051) sheds light on p53’s role in this phenomenon. Disturbed flow induces peroxynitrite production, which activates protein kinase C ζ and it’s binding to the E3 SUMO (small ubiquitin-like modifier) ligase PIASy (protein inhibitor of activated STATy). This leads to p53 SUMOylation and its export to the cytosol, where it binds to the antiapoptotic protein Bcl-2 to induce apoptosis.

Abstract 221: The P2x4 Receptor is Required for Neuroprotection via Ischemic Preconditioning

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Tomohiko Ozaki ◽  
Rieko Muramatsu ◽  
Toshiyuki Fujinaka ◽  
Toshiki Yoshimine ◽  
Toshihide Yamashita
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Vascular Endothelial Cells ◽  
Ischemic Tolerance ◽  
Receptor Expression ◽  
Vascular Endothelial ◽  
P2x4 Receptor ◽  
Flow Changes

Background: Ischemic preconditioning (IPC), a procedure consisting of transient ischemia and subsequent reperfusion, provides ischemic tolerance against prolonged ischemia in the brain. Although the blood flow changes mediated by IPC are primarily perceived by vascular endothelial cells, the role of these cells in ischemic tolerance has not fully clarified. In this research, we focused on the role of P2X4 receptor, which sense blood flow changes and is expressed on vascular endothelial cells. Methods: We administrated P2X4 receptor inhibitor into lateral ventricle of C57BL/6J male mice (8-10 weeks) and then conducted middle cerebral artery occlusion (MCAO). Fifteen minutes MCAO was done as IPC 48 hours before 60 minutes MCAO. To examine the necessity of P2X4 receptor expression in vascular endothelial cells, we generated a conditional knockout (CKO) mouse in which the P2X4 receptor was knocked down in VE-cadherin-positive vascular endothelial cells. To investigate molecular change by IPC, we obtained cerebrovascular endothelial cells of mice 48 hours after IPC, and real time PCR and ELISA were evaluated. To examine the molecular expression change on vascular endothelial cells by blood flow, we used in vitro culture system which generates fluid flow and real time PCR was evaluated. Inhibition of P2X4 receptor expression was conducted by P2X4 receptor siRNA transfection. Results: P2X4 receptor antagonist abolished neuroprotection via IPC. Moreover, the effect of IPC to P2X4 receptor CKO mice was smaller than control mice, the infarct volume of P2X4 receptor CKO was larger than control mice after 60 minutes MCAO (p<0.05, Control, n=4; CKO, n=6). IPC induced expression of osteopontin mRNA (p<0.05, n=5). Osteopontin administration attenuates the increase of infarct formation induced by P2X4 receptor inhibition (p<0.05, Control, n=5; Osteopontin, n=6). In vitro, shear stress upregulated expression of osteopontin mRNA (p<0.05, n=3). This upregulation was inhibited by P2X4 receptor siRNA (p<0.05, Control siRNA, n=6; P2X4 receptor siRNA, n=7). Conclusion: These results demonstrate a novel mechanism whereby vascular endothelial cells are involved in ischemic tolerance by way of the pathway about P2X4 receptor and osteopontin.

Revealing anti-inflammatory mechanisms of soy isoflavones by flow: modulation of leukocyte-endothelial cell interactions

2005 ◽  
Vol 289 (2) ◽  
pp. H908-H915 ◽  
Author(s):  
Balu K. Chacko ◽  
Robert T. Chandler ◽  
Ameya Mundhekar ◽  
Nicholas Khoo ◽  
Heather M. Pruitt ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Endothelial Cell ◽  
Vascular Endothelial Cells ◽  
Principal Component ◽  
Vascular Endothelial ◽  
Physical Forces ◽  
Anti Inflammatory ◽  
Static Conditions

The antiatherogenic effects of soy isoflavone consumption have been demonstrated in a variety of studies. However, the mechanisms involved remain poorly defined. Adhesion of monocytes to vascular endothelial cells is a key step within the inflammatory cascade that leads to atherogenesis. Many factors, including the physical forces associated with blood flow, regulate this process. Using an in vitro flow assay, we report that genistein, a principal component of most isoflavone preparations, inhibits monocyte adhesion to cytokine (TNF-α)-stimulated human vascular endothelial cells at physiologically relevant concentrations (0–1 μM). This effect is absolutely dependent on flow and is not observed under static conditions. Furthermore, this inhibition was dependent on activation of endothelial peroxisomal proliferator-activated receptor-γ. No significant role for other reported properties of genistein, including antioxidant effects, inhibition of tyrosine kinases, or activation of estrogen receptors, was observed. Furthermore, the antiadhesive effects of genistein did not occur via modulation of the adhesion molecules E-selectin, ICAM-1, VCAM-1, or platelet-endothelial cell adhesion molecule-1. These data reveal a novel anti-inflammatory mechanism for isoflavones and identify the physical forces associated with blood flow and a critical mediator of this function.

scholarly journals Exercise Inhibits Doxorubicin-Induced Damage to Cardiac Vessels and Activation of Hippo/YAP-Mediated Apoptosis

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2740
Author(s):  
Rong-Hua Tao ◽  
Masato Kobayashi ◽  
Yuanzheng Yang ◽  
Eugenie S. Kleinerman
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Blood Flow ◽  
Caspase 3 ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Wild Type ◽  
Major Side Effect ◽  
Cardiac Blood ◽  
Fractional Shortening

Dose-related cardiomyopathy is a major side effect following doxorubicin (Dox). To investigate whether exercise (Ex)-induced vasculogenesis plays a role in reducing Dox-induced cardiotoxicity, GFP+ bone marrow (BM) cells from GFP transgenic mice were transplanted into wild-type mice. Transplanted mice were treated with Dox, Ex, Dox+Ex, or control. We found Dox therapy resulted in decreased systolic and diastolic blood flow, decreased ejection fraction and fractional shortening, and decreased vascular endothelial cells and pericytes. These abnormalities were not seen in Dox+Ex hearts. Heart tissues from control-, Ex-, or Dox-treated mice showed a small number of GFP+ cells. By contrast, the Dox+Ex-treated hearts had a significant increase in GFP+ cells. Further analyses demonstrated these GFP+ BM cells had differentiated into vascular endothelial cells (GFP+CD31+) and pericytes (GFP+NG2+). Decreased cardiomyocytes were also seen in Dox-treated but not Dox+Ex-treated hearts. Ex induced an increase in GFP+c-Kit+ cells. However, these c-Kit+ BM stem cells had not differentiated into cardiomyocytes. Dox therapy induced phosphorylation of MST1/2, LATS1, and YAP; a decrease in total YAP; and cleavage of caspase-3 and PARP in the heart tissues. Dox+Ex prevented these effects. Our data demonstrated Dox-induced cardiotoxicity is mediated by vascular damage resulting in decreased cardiac blood flow and through activation of Hippo-YAP signaling resulting in cardiomyocyte apoptosis. Furthermore, Ex inhibited these effects by promoting migration of BM stem cells into the heart to repair the cardiac vessels damaged by Dox and through inhibiting Dox-induced Hippo-YAP signaling-mediated apoptosis. These data support the concept of using exercise as an intervention to decrease Dox-induced cardiotoxicity.

scholarly journals Potent Stimulation of Blood Flow in Fingers of Volunteers after Local Short-Term Treatment with Low-Frequency Magnetic Fields from a Novel Device

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Richard H. W. Funk ◽  
Lilla Knels ◽  
Antje Augstein ◽  
Rainer Marquetant ◽  
Hermann F. Dertinger
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Vascular Endothelial Cells ◽  
Low Frequency ◽  
Rapid Onset ◽  
Term Treatment ◽  
No Production ◽  
Vascular Endothelial ◽  
Short Term Treatment ◽  
Novel Device

A novel hand-held low-frequency magnetic stimulator (MagCell-SR) was tested for its ability to stimulate microcirculation in fingers of healthy volunteers. Blood flow during and after 5 minutes exposure was quantified using Laser Doppler Perfusion Imaging Technique. The device was positioned between the wrist and the dorsal part of the backhand. Because the increase in blood flow could be caused by a release of nitric oxide (NO) from the vascular endothelial cells we tested NO production with a fluorescence marker and quantified the measurements in cell cultures of human umbilical endothelial cells (HUVEC). Exposure increased blood flow significantly, persisted several minutes, and then disappeared gradually. In order to assess the effect of a static magnetic field, the measurements were also carried out with the device shutoff. Here, only a small increase in blood flow was noted. The application of the rotating MagCell-SR to the HUVEC cultures leads to a rapid onset and a significant increase of NO release after 15 minutes. Thus, frequencies between 4 and 12 Hz supplied by the device improve microcirculation significantly. Therefore, this device can be used in all clinical situations where an improvement of the microcirculation is useful like in chronic wound healing deficits.

scholarly journals Selective Requirements for Vascular Endothelial Cells and Circulating Factors in the Regulation of Retinal Neurogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Susov Dhakal ◽  
Shahar Rotem-Bamberger ◽  
Josilyn R. Sejd ◽  
Meyrav Sebbagh ◽  
Nathan Ronin ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Endothelial Cell ◽  
Cell Differentiation ◽  
Gas Exchange ◽  
Vascular System ◽  
Vascular Endothelial Cells ◽  
Retinal Development ◽  
Vascular Endothelial ◽  
Vertebrate Eye

Development of the vertebrate eye requires signaling interactions between neural and non-neural tissues. Interactions between components of the vascular system and the developing neural retina have been difficult to decipher, however, due to the challenges of untangling these interactions from the roles of the vasculature in gas exchange. Here we use the embryonic zebrafish, which is not yet reliant upon hemoglobin-mediated oxygen transport, together with genetic strategies for (1) temporally-selective depletion of vascular endothelial cells, (2) elimination of blood flow through the circulation, and (3) elimination of cells of the erythroid lineage, including erythrocytes. The retinal phenotypes in these genetic systems were not identical, with endothelial cell-depleted retinas displaying laminar disorganization, cell death, reduced proliferation, and reduced cell differentiation. In contrast, the lack of blood flow resulted in a milder retinal phenotype showing reduced proliferation and reduced cell differentiation, indicating that an endothelial cell-derived factor(s) is/are required for laminar organization and cell survival. The lack of erythrocytes did not result in an obvious retinal phenotype, confirming that defects in retinal development that result from vascular manipulations are not due to poor gas exchange. These findings underscore the importance of the cardiovascular system supporting and controlling retinal development in ways other than supplying oxygen. In addition, these findings identify a key developmental window for these interactions and point to distinct functions for vascular endothelial cells vs. circulating factors.

Shear type and magnitude affect aortic valve endothelial cell morphology, orientation, and differentiation

2021 ◽  
pp. 153537022110233
Author(s):  
Nandini Deb ◽  
Mir S Ali ◽  
Ashley Mathews ◽  
Ya-Wen Chang ◽  
Carla MR Lacerda
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Heart Valves ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Different Types ◽  
Mesenchymal Transformation

Valvular endothelial cells line the outer layer of heart valves and can withstand shear forces caused by blood flow. In contrast to vascular endothelial cells, there is limited amount of research over valvular endothelial cells. For this reason, the exact physiologic behavior of valvular endothelial cells is unclear. Prior studies have concluded that valvular endothelial cells align perpendicularly to the direction of blood flow, while vascular endothelial cells align parallel to blood flow. Other studies have suggested that different ranges of shear stress uniquely impact the behavior of valvular endothelial cells. The goal of this study was to characterize the response of valvular endothelial cell under different types, magnitudes, and durations of shear stress. In this work, the results demonstrated that with increased shear rate and duration of exposure, valvular endothelial cells no longer possessed the traditional cuboidal morphology. Instead through the change in cell circularity and aspect ratio, valvular endothelial cells aligned in an organized manner. In addition, different forms of shear exposure caused the area and circularity of valvular endothelial cells to decrease while inducing mesenchymal transformation validated through αSMA and TGFβ1 expression. This is the first investigation showing that valvular endothelial cells alignment is not as straightforward as once thought (perpendicular to flow). Different types and magnitudes of shear induce different local behaviors. This is also the first demonstration of valvular endothelial cells undergoing EndMT without chemical inducers on a soft surface in vitro. Findings from this study provide insights to understanding the pathophysiology of valvular endothelial cells which can potentially propel future artificial engineered heart valves.

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