scholarly journals Hypergravity Activates a Pro-Angiogenic Homeostatic Response by Human Capillary Endothelial Cells

2020 ◽  
Vol 21 (7) ◽  
pp. 2354 ◽  
Author(s):  
Chiara De Cesari ◽  
Ivana Barravecchia ◽  
Olga V. Pyankova ◽  
Matteo Vezza ◽  
Marco M. Germani ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Bed Rest ◽  
Tube Formation ◽  
Negative Effects ◽  
Sensitive Organ ◽  
Capillary Endothelial Cells ◽  
And Function ◽  
Disease Exposure ◽  
Dose Dependent Increase ◽  
Homeostatic Response

Capillary endothelial cells are responsible for homeostatic responses to organismic and environmental stimulations. When malfunctioning, they may cause disease. Exposure to microgravity is known to have negative effects on astronauts’ physiology, the endothelium being a particularly sensitive organ. Microgravity-related dysfunctions are striking similar to the consequences of sedentary life, bed rest, and ageing on Earth. Among different countermeasures implemented to minimize the effects of microgravity, a promising one is artificial gravity. We examined the effects of hypergravity on human microvascular endothelial cells of dermal capillary origin (HMEC-1) treated at 4 g for 15 min, and at 20 g for 15 min, 3 and 6 h. We evaluated cell morphology, gene expression and 2D motility and function. We found a profound rearrangement of the cytoskeleton network, dose-dependent increase of Focal Adhesion kinase (FAK) phosphorylation and Yes-associated protein 1 (YAP1) expression, suggesting cell stiffening and increased proneness to motility. Transcriptome analysis showed expression changes of genes associated with cardiovascular homeostasis, nitric oxide production, angiogenesis, and inflammation. Hypergravity-treated cells also showed significantly improved motility and function (2D migration and tube formation). These results, expanding our knowledge about the homeostatic response of capillary endothelial cells, show that adaptation to hypergravity has opposite effect compared to microgravity on the same cell type.

scholarly journals Endothelial cells and the IGF system

2014 ◽  
Vol 54 (1) ◽  
pp. R1-R13 ◽  
Author(s):  
Leon A Bach
Keyword(s):  
Endothelial Cells ◽  
Vascular Tone ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Tube Formation ◽  
Igf Binding Proteins ◽  
Igf System ◽  
Igf Binding ◽  
And Function ◽  
Cell Phenotypes

Endothelial cells line blood vessels and modulate vascular tone, thrombosis, inflammatory responses and new vessel formation. They are implicated in many disease processes including atherosclerosis and cancer. IGFs play a significant role in the physiology of endothelial cells by promoting migration, tube formation and production of the vasodilator nitric oxide. These actions are mediated by the IGF1 and IGF2/mannose 6-phosphate receptors and are modulated by a family of high-affinity IGF binding proteins. IGFs also increase the number and function of endothelial progenitor cells, which may contribute to protection from atherosclerosis. IGFs promote angiogenesis, and dysregulation of the IGF system may contribute to this process in cancer and eye diseases including retinopathy of prematurity and diabetic retinopathy. In some situations, IGF deficiency appears to contribute to endothelial dysfunction, whereas IGF may be deleterious in others. These differences may be due to tissue-specific endothelial cell phenotypes or IGFs having distinct roles in different phases of vascular disease. Further studies are therefore required to delineate the therapeutic potential of IGF system modulation in pathogenic processes.

scholarly journals Piezo1 is a mechanosensor channel in CNS capillaries

2021 ◽  
Vol 154 (9) ◽  
Author(s):  
Osama F. Harraz ◽  
Nicholas R. Klug ◽  
Amanda Senatore ◽  
Masayo Koide ◽  
Mark T. Nelson
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Ex Vivo ◽  
Outer Wall ◽  
Channel Blockers ◽  
Control Mechanisms ◽  
Hemodynamic Forces ◽  
Capillary Endothelial Cells ◽  
Patch Clamp Electrophysiology ◽  
And Function

Cerebral blood flow (CBF) is exquisitely controlled to meet the ever-changing demands of active neurons in the brain. Brain capillaries are equipped with sensors of neurovascular coupling agents released from neurons/astrocytes onto the outer wall of a capillary. While capillaries can translate external signals into electrical and Ca2+ changes, control mechanisms from the lumen are less clear. The continuous flux of red blood cells and plasma through narrow-diameter capillaries imposes mechanical forces on the luminal (inner) capillary wall. Whether—and, if so, how—the ever-changing CBF could be mechanically sensed in capillaries is not known. Here, we propose and provide evidence that the mechanosensitive Piezo1 channels operate as mechanosensors in CNS capillaries to ultimately regulate CBF. Patch clamp electrophysiology confirmed the expression and function of Piezo1 channels in brain cortical and retinal capillary endothelial cells. Mechanical or pharmacological activation of Piezo1 channels evoked currents that were sensitive to Piezo1 channel blockers. Using genetically encoded Ca2+ indicator (Cdh5-GCaMP8) mice, we observed that Piezo1 channel activation triggered Ca2+ signals in endothelial cells. An ex vivo pressurized retina preparation was employed to further explore the mechanosensitivity of capillary Piezo1-mediated Ca2+ signals. Genetic and pharmacologic manipulation of Piezo1 in endothelial cells had significant impacts on CBF, reemphasizing the crucial role of mechanosensation in blood flow control. In conclusion, this study shows that Piezo1 channels act as mechanosensors in capillaries, and that these channels initiate crucial Ca2+ signals. We further show that Piezo1 modulates CBF, an observation of profound significance for the control of brain blood flow in health and in disorders where hemodynamic forces are disrupted, such as hypertension.

scholarly journals Expression of prolactin mRNA and of prolactin-like proteins in endothelial cells: evidence for autocrine effects

1998 ◽  
Vol 158 (1) ◽  
pp. 137-144 ◽  
Author(s):  
C Clapp ◽  
FJ Lopez-Gomez ◽  
G Nava ◽  
A Corbacho ◽  
L Torner ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Messenger Rna ◽  
Tube Formation ◽  
Bovine Brain ◽  
Nb2 Cells ◽  
Prolactin Gene ◽  
Capillary Endothelial Cells ◽  
Molecular Masses ◽  
Antiangiogenic Factors

Formation of new capillary blood vessels, termed angiogenesis, is essential for the growth and development of tissues and underlies a variety of diseases including tumor growth. Members of the prolactin hormonal family bind to endothelial cell receptors and have direct effects on cell proliferation, migration and tube formation. Because many angiogenic and antiangiogenic factors are produced by endothelial cells, we investigated whether endothelial cells expressed the prolactin gene. Here we show that bovine brain capillary endothelial cells (BBCEC) in culture express the full-length prolactin messenger RNA, in addition to a novel prolactin transcript, lacking the third exon of the gene. In addition cultures of BBCEC synthesize and secrete prolactin-like immunoreactive proteins with apparent molecular masses of 23, 21 and 14 kDa. The prolactin-like nature of these proteins in supported by the observation that Nb2-cells, a prolactin-responsive cell line, were stimulated to proliferate when co-cultured with endothelial cells and this stimulation was neutralized with prolactin-directed antibodies. Finally, consistent with a possible autocrine effect of endothelial-derived prolactins, polyclonal and monoclonal prolactin antibodies specifically inhibited basal and basis fibroblast growth-factor-stimulated growth of endothelial cells. Taken together, the present findings support the hypothesis of the prolactin gene being expressed in endothelial cells as proteins that could act in an autocrine fashion to regulate cell proliferation.

scholarly journals TRPV4 regulates migration and tube formation of human retinal capillary endothelial cells

2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Lei Wen ◽  
Yue-Chun Wen ◽  
Gen-Jie Ke ◽  
Si-Qin Sun ◽  
Kai Dong ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tube Formation ◽  
Retinal Capillary ◽  
Capillary Endothelial Cells

scholarly journals Hu-Zhang-Qing-Mai-Yin Inhibits Proliferation of Human Retinal Capillary Endothelial Cells Exposed to High Glucose

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuan-Yuan Yu ◽  
Qiu-Ping Liu ◽  
Meng-Ting Li ◽  
Pei An ◽  
Yu-Ying Chen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Western Blot ◽  
Effective Treatment ◽  
Signaling Pathway ◽  
High Glucose ◽  
Tube Formation ◽  
Chemical Components ◽  
Dependent Manner ◽  
Retinal Capillary ◽  
Capillary Endothelial Cells

Background: Diabetic retinopathy (DR) is one of the serious complications of diabetes and an important cause of blindness. Despite much research on the pathogenesis of DR, there is still a lack of safe and effective treatment methods. Hu-zhang-qing-mai-yin (HZQMY), a Chinese medicine formula, has been clinically used in the safe and effective treatment of DR for many years. However, the systematic pharmacological research is lacking. The aim of this study was to evaluate the anti-DR effects of HZQMY and explore the possible mechanism involved. Methods: The constituents of HZQMY were analyzed by LC-MS/MS. DR model was established by high glucose simulation on human retinal capillary endothelial cells (HRCECs) in vitro. The cell viability, cell proliferation, cell apoptosis, and tube formation were assessed. Subsequently the related mechanisms were analyzed by assays for JC-1 mitochondrial membrane potential (MMP), intracellular ROS, ATP, western blot and proteomics. Results: 27 main chemical components contained in HZQMY were identified. HZQMY significantly inhibited the viability and proliferation of HRCECs exposed to high glucose, and promoted the apoptosis. In addition, HZQMY also boosted the release of ROS and suppressed tube formation of HRCECs under high glucose exposure. Meanwhile, HRCECs treated with high glucose released more ROS than normal cells, which could be markedly inhibited by HZQMY in a dose-dependent manner. Additionally, western blot assay indicated that HZQMY increased the expression of proteins related to the P38 signaling pathway and inhibited nuclear factor kappa-B (NF-κB) pathway. Proteomic analysis predicted that HSPA4, MAPK3, ENO1, EEF2 and ERPS may be the candidate targets of HZQMY in HRCECs. Conclusions: HZQMY inhibited the proliferation and promoted the Mitochondria related apoptosis of HRCECs exposed to high glucose possibly through regulating P38 and NF-κB signaling pathway.

scholarly journals Primary tumor- and metastasis-derived colon cancer cells differently modulate connexin expression and function in human capillary endothelial cells

Oncotarget ◽  
2015 ◽  
Vol 6 (30) ◽  
pp. 28800-28815 ◽  
Author(s):  
Dominique Thuringer ◽  
Kevin Berthenet ◽  
Laurent Cronier ◽  
Eric Solary ◽  
Carmen Garrido
Keyword(s):  
Colon Cancer ◽  
Endothelial Cells ◽  
Cancer Cells ◽  
Primary Tumor ◽  
Colon Cancer Cells ◽  
Connexin Expression ◽  
Capillary Endothelial Cells ◽  
And Function

Abstract 5440: Klf2 Inhibits Hif-1α Expression and Function in the Endothelium

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Daiji Kawanami ◽  
Zhiyong Lin ◽  
Ganapati Mahabaleshwar ◽  
G. B Atkins ◽  
Anne Hamik ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Hypoxia Inducible Factor ◽  
Proteasome Inhibitors ◽  
Cell Types ◽  
Tube Formation ◽  
Protein Levels ◽  
Umbilical Vein Endothelial Cells ◽  
And Function ◽  
Mediated Reduction

Introduction: Hypoxia-inducible factor 1 (HIF-1) is a central regulator of the hypoxic response in many cell types. In endothelial cells, HIF-1 induces the expression of key pro-angiogenic factors such as vascular endothelial growth factor (VEGF) to induce new blood vessel formation. Recent studies have identified Kruppel-like Factor 2 (KLF2) as a potent inhibitor of angiogenesis. However, the role of KLF2 in regulating the expression and function of HIF-1 has not been evaluated. Hypothesis: KLF2 inhibits HIF-1α expression and function. Methods and Results: Adenoviral overexpression of KLF2 in human umbilical vein endothelial cells (HUVECs) inhibited hypoxia-induced expression of HIF-1α, VEGF secretion, and matrigel tube formation. Conversely, siRNA-mediated knockdown of KLF2 in HUVECs increased HIF-1α expression and VEGF secretion. Consistent with this observation, KLF2−/− mouse embryonic fibroblasts (MEFs) showed accelerated HIF-1α accumulation in response to hypoxia and a marked induction of VEGF secretion (90.4±7.4 pg/ml in KLF2+/+ versus 234.6±6.1 pg/ml in KLF2−/−, p<0.01). From a mechanistic standpoint, KLF2-mediated reduction of HIF-1α level was attenuated by three distinct proteasome inhibitors (MG132, ALLN, or lactacystin), demonstrating that KLF2 mediated reduction of HIF-1α protein was proteasome-dependent. In addition, KLF2 maintained its ability to inhibit HIF-1α protein levels in VHL−/− cells, thermo-sensitive E1 deficient cells, and p53−/− cells. Finally, co-immunoprecipitation experiments revealed that KLF2 overexpression disrupted the interaction between HIF-1α and its chaperone Hsp90, suggesting that KLF2 promotes degradation of HIF-1α by affecting its folding and maturation. Conclusions: These observations identify KLF2 as a novel inhibitor of HIF-1α expression and function through a VHL/p53 independent but proteasome dependent pathway. As such, KLF2 may be a target for modulating the angiogenic response in disease states.

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