scholarly journals Cytoskeletal Remodeling Mimics Endothelial Response to Microgravity

2021 ◽  
Vol 9 ◽  
Author(s):  
Laura Locatelli ◽  
Jeanette A. M. Maier
Keyword(s):  
Endothelial Cells ◽  
Stress Response ◽  
Actin Polymerization ◽  
Simulated Microgravity ◽  
Transient Receptor Potential ◽  
Vascular Endothelial Cells ◽  
Cytochalasin D ◽  
Endothelial Cell Proliferation ◽  
Vascular Endothelial ◽  
Transient Receptor Potential Melastatin

Mechanical cues contribute to the maintenance of a healthy endothelium, which is essential for vascular integrity. Indeed endothelial cells are mechanosensors that integrate the forces in the form of biochemical signals. The cytoskeleton is fundamental in sensing mechanical stimuli and activating specific signaling pathways. Because the cytoskeleton is very rapidly remodeled in endothelial cells exposed to microgravity, we investigated whether the disruption of actin polymerization by cytochalasin D in 1g condition triggers and orchestrates responses similar to those occurring in micro- and macro-vascular endothelial cells upon gravitational unloading. We focused our attention on the effect of simulated microgravity on stress proteins and transient receptor potential melastatin 7 (TRPM7), a cation channel that acts as a mechanosensor and modulates endothelial cell proliferation and stress response. Simulated microgravity downregulates TRPM7 in both cell types. However, 24 h of treatment with cytochalasin D decreases the amounts of TRPM7 only in macrovascular endothelial cells, suggesting that the regulation and the role of TRPM7 in microvascular cells are more complex than expected. The 24 h culture in the presence of cytochalasin D mimics the effect of simulated microgravity in modulating stress response in micro- and macro-vascular endothelial cells. We conclude that cytoskeletal disruption might mediate some effects of microgravity in endothelial cells.

scholarly journals TRPM7 regulates vascular endothelial cell adhesion and tube formation

2015 ◽  
Vol 308 (4) ◽  
pp. C308-C318 ◽  
Author(s):  
Zhao Zeng ◽  
Koichi Inoue ◽  
Huawei Sun ◽  
Tiandong Leng ◽  
Xuechao Feng ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Transient Receptor Potential ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Underlying Mechanism ◽  
Tube Formation ◽  
Vascular Endothelial ◽  
Cell Contractility ◽  
Transient Receptor Potential Melastatin

Transient receptor potential melastatin 7 (TRPM7) is a nonselective cation channel with an α-kinase domain in its COOH terminal, known to play a role in diverse physiological and pathological processes such as Mg2+ homeostasis, cell proliferation, and hypoxic neuronal injury. Increasing evidence suggests that TRPM7 contributes to the physiology/pathology of vascular systems. For example, we recently demonstrated that silencing TRPM7 promotes growth and proliferation and protects against hyperglycemia-induced injury in human umbilical vein endothelial cells (HUVECs). Here we investigated the potential effects of TRPM7 on morphology, adhesion, migration, and tube formation of vascular endothelial cells and the potential underlying mechanism. We showed that inhibition of TRPM7 function in HUVECs by silencing TRPM7 decreases the density of TRPM7-like current and cell surface area and inhibits cell adhesion to Matrigel. Silencing TRPM7 also promotes cell migration, wound healing, and tube formation. Further studies showed that the extracellular signal-regulated kinase (ERK) pathway is involved in the change of cell morphology and the increase in HUVEC migration induced by TRPM7 silencing. We also demonstrated that silencing TRPM7 enhances the phosphorylation of myosin light chain (MLC) in HUVECs, which might be involved in the enhancement of cell contractility and motility. Collectively, our data suggest that the TRPM7 channel negatively regulates the function of vascular endothelial cells. Further studies on the underlying mechanism may facilitate the development of the TRPM7 channel as a target for the therapeutic intervention of vascular diseases.

scholarly journals Negative correlation between endoglin levels and coronary atherosclerosis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Haibin Chen ◽  
Yiping Wang ◽  
Bing Sun ◽  
Xunxia Bao ◽  
Yu Tang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Coronary Atherosclerosis ◽  
Transforming Growth Factor ◽  
Vascular Endothelial Cells ◽  
Expression Profiles ◽  
Receptor Protein ◽  
Inflammatory Factors ◽  
Endothelial Cell Proliferation ◽  
Vascular Endothelial ◽  
Smad Pathway

Abstract Background Coronary artery disease (CAD) is a common cardiovascular disease, and abnormal blood lipid metabolism is an important risk factor. Transforming growth factor-ß (TGF-ß) and its receptor (TGF-ßR) can inhibit the release of inflammatory factors through the SMAD pathway-mediated immune response, thereby suppressing the progression of CAD. Endoglin (TGF-ßRIII), a TGF-ßR family homologous receptor protein, is directly involved in the immunoregulatory process, but the exact mechanism is unclear. This study aimed to clarify the pathophysiological effects of endoglin on the development of atherosclerosis and to explore the mechanism of the signalling pathway. Methods We downloaded the GEO dataset to perform a functional analysis of SMAD family activity and TGF-ß receptor protein expression in the monocyte expression profiles of patients with familial hyperlipidaemia (FH). The effect of endoglin on endothelial cell proliferation, migration, and apoptosis was examined by disrupting the endoglin gene in human umbilical vein endothelial cells (HUVECs) and validated by western blotting. The related genes and pathways regulated by endoglin were obtained by analysing the sequencing data. Results Research has shown that interference with endoglin can promote the proliferation and migration and significantly inhibit the apoptosis of vascular endothelial cells. Interference with endoglin particularly encourages the expression of VEGFB in vascular endothelial cells. Conclusion The endoglin gene in vascular endothelial cells regulates the PI3K-Akt, Wnt, TNF, and cellular metabolism pathways by activating the SMAD pathway. RAB26, MR1, CCL2, SLC29A4, IBTK, VEGFB, and GOLGA8B play critical roles. Endoglin interacts closely with 11 proteins such as CCL2 and SEPRINE1, which participate in the vital pathway of plaque formation. Interference with endoglin can alter the course of coronary atherosclerosis.

scholarly journals Altered Functions of Human Blood-Derived Vascular Endothelial Cells by Simulated Microgravity

2020 ◽  
Vol 4 (1) ◽  
pp. 2-16
Author(s):  
Vidhya Ramaswamy ◽  
Allison Goins ◽  
Josephine B. Allen
Keyword(s):  
Endothelial Cells ◽  
Human Blood ◽  
Simulated Microgravity ◽  
Cardiovascular Health ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Altered Gravity ◽  
Adaptation Mechanism ◽  
Insight Into

AbstractRecently, the increase in incidence of cardiovascular degeneration associated with weightlessness has drawn much attention to the detrimental effects of space travel on cardiovascular health. Particularly, the regulatory role of the endothelium in cardiovascular degeneration has been studied extensively. The goal of this study was to understand the effects of simulated microgravity on the proliferative, secretory, and anti-thrombogenic functions of endothelial cells differentiated from human blood-derived progenitor cells. Exposure to simulated microgravity enhanced proliferation, as well as the release of soluble nitric oxide while downregulating the release of pro-inflammatory cytokines, such as interleukin-6 (IL-6). Interestingly, the cells also upregulated gene expression of heat shock protein 70 (hsp70), which may be a potential adaptation mechanism of the cells to altered gravity conditions. However, the secretory and proliferative functions had no effect on the anti-thrombogenic functions of these cells. Their anti-coagulative and anti-thrombogenic abilities, as assessed by both upregulation of tissue plasminogen activator (tPA) and their ability to delay plasma clotting, were impaired on exposure to simulated microgravity. These results collectively provide a useful insight into various mechanisms involved in regulating anti-thrombogenic ability of the endothelium, as well as cardiovascular health in altered gravity conditions.

scholarly journals Effects of Simulated Microgravity on Ultrastructure and Apoptosis of Choroidal Vascular Endothelial Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Hongwei Zhao ◽  
Yuanyuan Shi ◽  
Changyu Qiu ◽  
Jun Zhao ◽  
Yubo Gong ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cytochrome C ◽  
Protein Expression ◽  
Simulated Microgravity ◽  
Vascular Endothelial Cells ◽  
Chromatin Condensation ◽  
Microgravity Condition ◽  
Vascular Endothelial ◽  
Apoptosis Pathway ◽  
Mrna And Protein Expression

BackgroundIt was confirmed that simulated microgravity (SMG) led to ultrastructural alterations and apoptosis in many types of microvascular endothelial cells. However, whether SMG would also affect choroidal vascular endothelial cells (CVECs) remains unknown. This study was designed to investigate the effects of SMG on ultrastructure and apoptosis of CVECs.MethodsThe rotary cell culture system (RCCS) was utilized to simulate microgravity condition. Human CVECs were cultured under normal gravity (NG) or SMG condition for 3 days. The ultrastructure was viewed under transmission electron microscopy, and the organization of F-actin was observed by immunofluorescence staining. Additionally, the apoptosis percentage was calculated using flow cytometry. Moreover, the mRNA and protein expression of BAX, Bcl-2, Caspase3, Cytochrome C, p-AKT, and p-PI3K were detected with quantitative PCR and Western blot at different exposure time.ResultsIn the SMG group, CVECs presented with a shrunk cell body, chromatin condensation and margination, mitochondria vacuolization, and apoptotic bodies. The amount of F-actin decreased, and the filaments of F-actin were sparse or even partly discontinuous after cultivation under SMG for 72 h. The proportions of apoptotic CVECs in SMG groups at 24 and 72 h were significantly higher than those in the NG group (P < 0.001). The mRNA and protein expression of Bax, Caspase3, and Cytochrome C of CVECs in SMG groups at 24 and 72 h significantly increased than those of the NG group, respectively (P < 0.001). The alterations of p-AKT and p-PI3K protein expression possessed similar trends. On the contrary, the mRNA and protein expression of Bcl-2 in CVECs under SMG at 24 and 72 h were significantly less than that of the NG group, respectively (P < 0.001).ConclusionSimulated microgravity conditions can lead the alterations of the F-actin structure and apoptosis of CVECs. The Bcl-2 apoptosis pathway and PI3K/AKT pathway may participate in the damage of CVECs caused by SMG.

scholarly journals Mechanism of temporal gradients in shear-induced ERK1/2 activation and proliferation in endothelial cells

2001 ◽  
Vol 281 (1) ◽  
pp. H22-H29 ◽  
Author(s):  
Xuping Bao ◽  
Chuanyi Lu ◽  
John A. Frangos
Keyword(s):  
Endothelial Cells ◽  
Intracellular Signaling ◽  
Proliferative Response ◽  
Vascular Endothelial Cells ◽  
Inhibitory Effect ◽  
Steady Shear ◽  
Endothelial Cell Proliferation ◽  
Vascular Endothelial ◽  
Extracellular Signal ◽  
Intracellular Signaling Cascade

The aim of the current study was to investigate the intracellular signaling cascade that leads to temporal gradients in shear (TGS)-induced endothelial cell proliferation, with a focus on the involvement of extracellular signal-regulated kinases 1 and 2 (ERK1/2). With the use of well-defined pulsatile, impulse, step, and ramp laminar flow profiles, we found that TGS (impulse flow and pulsatile flow) induced an enhanced and sustained (>30 min) phosphorylation of ERK1/2 relative to step flow (which contains a step increase in shear followed by steady shear), whereas steady shear (ramp flow) alone downregulated activated ERK1/2. Nitric oxide (NO) was found to mediate both the stimulatory effect of TGS and the inhibitory effect of steady shear on endothelial ERK1/2 phosphorylation. Reactive oxygen species (ROS) were also demonstrated to be associated with TGS-induced ERK1/2 phosphorylation. Both Gq/11 and Gi3 were necessary for the activation of ERK1/2 by TGS. Finally, the TGS-induced endothelial proliferative response was abolished by ERK1/2 inhibition. Our study demonstrated the essential role of G proteins, NO, and ROS in TGS-dependent ERK1/2 activation and proliferative response in vascular endothelial cells.

scholarly journals Hepatitis B Virus preS2 Domain Promotes Angiogenesis in Hepatocellular Carcinoma via Transcriptional Activation of VEGFA Promoter

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fang Luan ◽  
Bin Liu ◽  
Xiangrui Guo ◽  
Wang Yong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Endothelial Cells ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Vascular Endothelial Cells ◽  
Luciferase Assay ◽  
Luciferase Reporter ◽  
Endothelial Cell Proliferation ◽  
Vascular Endothelial ◽  
B Virus

: Angiogenesis is closely related to the development and progression of hepatocellular carcinoma (HCC). Angiogenic factors have been confirmed to be overexpressed in HCC. The hepatitis B virus preS2 domain is a transactivator that plays an important role in hepatitis B virus (HBV)-related HCC. Here, we aimed to investigate the potential of the preS2 domain in inducing angiogenesis in HCC. A total of 25 cases of pathologically confirmed HCC were screened. The levels of preS2, CD34, and vascular endothelial growth factor A (VEGFA) in HCC samples were evaluated by immunohistochemistry (IHC). The proliferation of vascular endothelial cells was detected by CCK-8. Besides, VEGFA was analyzed by Western blot in HCC cells. The effect of preS2 on the VEGFA promoter was measured by dual-luciferase reporter assays. We found that preS2 domain-positive HCCs had significantly higher microvessel density (MVD) and VEGFA expression than preS2 domain-negative HCCs. Overexpression of preS2 upregulated VEGFA expression in HepG2 and activated vascular endothelial cell proliferation. However, blocking preS2 expression reduced VEGFA expression in HepG2.2.15 and inhibited the proliferation of vascular endothelial cells. In addition, a dual-luciferase assay indicated that the preS2 domain could activate VEGFA promoter activity. In conclusion, we showed that the expression of the preS2 domain promotes angiogenesis by transactivating the VEGFA promoter in HCC.

Clinorotation enhances autophagy in vascular endothelial cells

2013 ◽  
Vol 91 (5) ◽  
pp. 309-314 ◽  
Author(s):  
Yong-Chun Wang ◽  
Dong-Yuan Lu ◽  
Fei Shi ◽  
Shu Zhang ◽  
Chang-Bin Yang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Simulated Microgravity ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Bed Rest ◽  
Degradation Pathway ◽  
Vascular Endothelial ◽  
Autophagosome Formation ◽  
Umbilical Vein Endothelial Cells ◽  
Adaptive Role

Individuals exposed to extended periods of spaceflight or prolonged 6° head-down-tilt bed rest often suffer from health hazards represented by cardiovascular deconditioning. Many studies have reported that alterations in vascular endothelial cells contribute to cardiovascular dysfunction induced by microgravity. Autophagy, a lysosomal degradation pathway, serves an adaptive role for survival, differentiation, and development in cellular homeostasis, and can be triggered by various environmental stimuli. However, whether autophagy can be induced in endothelial cells by real or simulated microgravity remains to be determined. This study was designed to investigate the effects of simulated microgravity on the activation of autophagy in human umbilical vein endothelial cells (HUVECs). We report here that clinorotation, a simulated model of microgravity, enhances autophagosome formation, increases LC3 and beclin-1 expression, and promotes the conversion of LC3-I to LC3-II in HUVECs. These results demonstrate that simulated microgravity for 48 h activates autophagy of vascular endothelial cells.

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