Switch in Laminin β2 to Laminin β1 Isoforms During Aging Controls Endothelial Cell Functions—Brief Report

Gold nanoparticles (AuNPs) are used for diagnostic and therapeutic purposes, especially antiangiogenesis, which are accomplished via inhibition of endothelial cell proliferation, migration, and tube formation. However, no research has been performed on the effects of AuNPs in pericytes, which play vital roles in endothelial cell functions and capillary tube formation during physiological and pathological processes. Therefore, the effects of AuNPs on the morphology and functions of pericytes need to be elucidated. This study treated human placental pericytes in monoculture with 20 nm AuNPs at a concentration of 30 ppm. Ki-67 and platelet-derived growth factor receptor-β (PDGFR-β) mRNA expression was measured using real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell migration was assessed by Transwell migration assay. The fine structures of pericytes were observed by transmission electron microscopy. In addition, 30 ppm AuNP-treated pericytes and intact human umbilical vein endothelial cells were cocultured on Matrigel to form three-dimensional (3D) capillary tubes. The results demonstrated that AuNPs significantly inhibited proliferation, reduced PDGFR-β mRNA expression, and decreased migration in pericytes. Ultrastructural analysis of pericytes revealed AuNPs in late endosomes, autolysosomes, and mitochondria. Remarkably, many mitochondria were swollen or damaged. Additionally, capillary tube formation was reduced. We found that numerous pericytes on 3D capillary tubes were round and did not extend their processes along the tubes, which resulted in more incomplete tube formation in the treatment group compared with the control group. In summary, AuNPs can affect pericyte proliferation, PDGFR-β mRNA expression, migration, morphology, and capillary tube formation. The findings highlight the possible application of AuNPs in pericyte-targeted therapy for antiangiogenesis.

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Atorvastatin disrupts primary human brain microvascular endothelial cell functions via prenylation‐dependent mitochondrial inhibition and oxidative stress

Fundamental and Clinical Pharmacology ◽

10.1111/fcp.12615 ◽

2020 ◽

Author(s):

Qian Tan ◽

Danfang Yu ◽

Lin Song

Keyword(s):

Oxidative Stress ◽

Endothelial Cell ◽

Human Brain ◽

Microvascular Endothelial Cell ◽

Brain Microvascular Endothelial Cell ◽

Cell Functions ◽

Microvascular Endothelial ◽

And Oxidative Stress

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An autoantibody directed against human thrombin anion-binding exosite in a patient with arterial thrombosis: effects on platelets, endothelial cells, and protein C activation

Blood ◽

10.1182/blood.v84.6.1843.1843 ◽

1994 ◽

Vol 84 (6) ◽

pp. 1843-1850 ◽

Cited By ~ 14

Author(s):

E Arnaud ◽

M Lafay ◽

P Gaussem ◽

V Picard ◽

M Jandrot-Perrus ◽

...

Keyword(s):

Endothelial Cells ◽

Endothelial Cell ◽

Arterial Thrombosis ◽

Protein C ◽

Receptor Activation ◽

Anion Binding ◽

Thrombin Receptor ◽

Cell Functions ◽

Human Thrombin

Abstract An autoantibody, developed by a patient with severe and recurrent arterial thrombosis, was characterized to be directed against the anion- binding exosite of thrombin, and inhibited all thrombin interactions requiring this secondary binding site without interfering with the catalytic site. The effect of the antibody was studied on thrombin interactions with platelets and endothelial cells from human umbilical veins (HUVEC). The autoantibody specifically and concentration- dependently inhibited alpha-thrombin-induced platelet activation and prostacyclin (PGI2) synthesis from HUVEC. It had no effect when gamma- thrombin or the thrombin receptor activation peptide SFLLR were the inducers. The effect of the antibody on protein C activation has been studied. The antibody blocked the thrombin-thrombomodulin activation of protein C. The inhibition of the activation was maximal with a low concentration of thrombomodulin. The fact that the autoantibody inhibited concentration-dependent alpha-thrombin-induced platelet and endothelial cell functions emphasizes the crucial role of the anion- binding exosite of thrombin to activate its receptor. In regard to the pathology, the antibody inhibited two vascular processes implicated in thrombin-antithrombotic functions, PGI2 secretion, and protein C activation, which could be implicated in this arterial thrombotic disease.

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miR-27b Suppresses Endothelial Cell Proliferation and Migration by Targeting Smad7 in Kawasaki Disease

Cellular Physiology and Biochemistry ◽

10.1159/000492354 ◽

2018 ◽

Vol 48 (4) ◽

pp. 1804-1814 ◽

Cited By ~ 9

Author(s):

Xing Rong ◽

Donghui Ge ◽

Danping Shen ◽

Xianda Chen ◽

Xuliang Wang ◽

...

Keyword(s):

Endothelial Cell ◽

Kawasaki Disease ◽

Therapeutic Target ◽

Umbilical Vein ◽

Luciferase Reporter ◽

Endothelial Cell Proliferation ◽

Cell Functions ◽

Potential Biomarker ◽

And Migration ◽

Proliferation And Migration

Background/Aims: Increasing evidence indicates that microRNAs (miRNAs) play important roles in Kawasaki disease (KD). Our previous study demonstrated that hsa-miR-27b-3p (miR-27b) was up-regulated in KD serum. However, the specific role of miR-27b in KD remains unclear. We aimed to investigate that miR-27b could be a biomarker and therapeutic target for KD treatment. As well, the specific mechanism of miR-27b effecting endothelial cell functions was studied. Methods: The expression of miR-27b and Smad7 was measured by qRT-PCR. Gain-of-function strategy was used to observe the effect of miR-27b on human umbilical vein endothelial cells (HUVECs) proliferation and migration. Bioinformatics analyses were applied to predict miR-27b targets and then we verified Smad7 by a luciferase reporter assay. Western blot was performed to detect the protein expression of Smad7, PCNA, MMP9, MMP12 and TGF-β-related genes. Results: We confirmed that miR-27b was shown to be dramatically up-regulated in KD serum and KD serum-treated HUVECs and that elevated expression of miR-27b suppressed the proliferation and migration of HUVECs. Furthermore, our results verified that miR-27b mediated cell functions by affecting the TGF-β via targeting Smad7 in HUVECs. Conclusion: These results suggested that up-regulated miR-27b had a protective role in HUVECs proliferation and migration via targeting Smad7 and affecting TGF-β pathway. Therefore, miR-27b represented a potential biomarker for KD and may serve as a promising therapeutic target for KD treatment.

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Polyphyllin D, a steroidal saponin from Paris polyphylla, inhibits endothelial cell functions in vitro and angiogenesis in zebrafish embryos in vivo

Journal of Ethnopharmacology ◽

10.1016/j.jep.2011.04.021 ◽

2011 ◽

Vol 137 (1) ◽

pp. 64-69 ◽

Cited By ~ 35

Author(s):

Judy Yuet-Wa Chan ◽

Johnny Chi-Man Koon ◽

Xiaozhou Liu ◽

Michael Detmar ◽

Biao Yu ◽

...

Keyword(s):

Endothelial Cell ◽

Zebrafish Embryos ◽

Steroidal Saponin ◽

Cell Functions ◽

Paris Polyphylla ◽

Polyphyllin D

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Receptor and Molecular Mechanism of AGGF1 Signaling in Endothelial Cell Functions and Angiogenesis

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.121.316867 ◽

2021 ◽

Author(s):

Jingjing Wang ◽

Huixin Peng ◽

Ayse Anil Timur ◽

Vinay Pasupuleti ◽

Yufeng Yao ◽

...

Keyword(s):

Amino Acids ◽

Endothelial Cell ◽

Neutralizing Antibodies ◽

Molecular Mechanisms ◽

Capillary Tube ◽

Therapeutic Angiogenesis ◽

Angiogenic Factor ◽

Single Amino Acid ◽

Binding Motif ◽

Cell Functions

Objective: Angiogenic factor AGGF1 (angiogenic factor and G-patch and FHA [Forkhead-associated] domain 1) promotes angiogenesis as potently as VEGFA (vascular endothelial growth factor A) and regulates endothelial cell (EC) proliferation, migration, specification of multipotent hemangioblasts and venous ECs, hematopoiesis, and vascular development and causes vascular disease Klippel-Trenaunay syndrome when mutated. However, the receptor for AGGF1 and the underlying molecular mechanisms remain to be defined. Approach and Results: Using functional blocking studies with neutralizing antibodies, we identified α5β1 as the receptor for AGGF1 on ECs. AGGF1 interacts with α5β1 and activates FAK (focal adhesion kinase), Src, and AKT. Functional analysis of 12 serial N-terminal deletions and 13 C-terminal deletions by every 50 amino acids mapped the angiogenic domain of AGGF1 to a domain between amino acids 604-613 (FQRDDAPAS). The angiogenic domain is required for EC adhesion and migration, capillary tube formation, and AKT activation. The deletion of the angiogenic domain eliminated the effects of AGGF1 on therapeutic angiogenesis and increased blood flow in a mouse model for peripheral artery disease. A 40-mer or 15-mer peptide containing the angiogenic domain blocks AGGF1 function, however, a 15-mer peptide containing a single amino acid mutation from −RDD- to −RGD- (a classical RGD integrin-binding motif) failed to block AGGF1 function. Conclusions: We have identified integrin α5β1 as an EC receptor for AGGF1 and a novel AGGF1-mediated signaling pathway of α5β1-FAK-Src-AKT for angiogenesis. Our results identify an FQRDDAPAS angiogenic domain of AGGF1 crucial for its interaction with α5β1 and signaling.

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The Role of the Vascular Endothelial Growth Factor–Delta-like 4 Ligand/Notch4-Ephrin B2 Cascade in Tumor Vessel Remodeling and Endothelial Cell Functions

Cancer Research ◽

10.1158/0008-5472.can-05-4226 ◽

2006 ◽

Vol 66 (17) ◽

pp. 8501-8510 ◽

Cited By ~ 120

Author(s):

Patricia Hainaud ◽

Jean-Olivier Contrerès ◽

Aude Villemain ◽

Lang-Xia Liu ◽

Jean Plouët ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Endothelial Cell ◽

Growth Factor ◽

Vascular Endothelial ◽

Tumor Vessel ◽

Cell Functions ◽

Vessel Remodeling ◽

Endothelial Growth Factor

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Nobiletin, a citrus polymethoxyflavonoid, suppresses multiple angiogenesis-related endothelial cell functions and angiogenesis in vivo

Cancer Science ◽

10.1111/j.1349-7006.2010.01668.x ◽

2010 ◽

Vol 101 (11) ◽

pp. 2462-2469 ◽

Cited By ~ 34

Author(s):

Kazuhiro Kunimasa ◽

Masahiko Ikekita ◽

Mayumi Sato ◽

Toshiro Ohta ◽

Yukio Yamori ◽

...

Keyword(s):

Endothelial Cell ◽

Cell Functions

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VEGF-C mediates cyclic pressure-induced endothelial cell proliferation

Physiological Genomics ◽

10.1152/physiolgenomics.00068.2002 ◽

2002 ◽

Vol 11 (3) ◽

pp. 245-251 ◽

Cited By ~ 33

Author(s):

Hainsworth Y. Shin ◽

Michael L. Smith ◽

Karen J. Toy ◽

P. Mickey Williams ◽

Rena Bizios ◽

...

Keyword(s):

Endothelial Cell ◽

Growth Factor ◽

Gene Transcription ◽

Molecular Mechanisms ◽

Transforming Growth Factor ◽

Umbilical Vein ◽

Culture Conditions ◽

Endothelial Cell Proliferation ◽

Cyclic Pressure ◽

Cell Functions

Mechanical forces modulate endothelial cell functions through several mechanisms including regulation of gene transcription. In the present study, gene transcription by human umbilical vein endothelial cells (HUVEC) either maintained under control pressure (that is, standard cell culture conditions equivalent to 0.15 mmHg sustained hydrostatic pressure) or exposed to 60/20 mmHg sinusoidal pressures at 1 Hz were compared using Affymetrix GeneChip microarrays to identify cellular/molecular mechanisms associated with endothelial cell responses to cyclic pressure. Cyclic pressure selectively affected transcription of 14 genes that included a set of mechanosensitive proteins involved in hemostasis (tissue plasminogen activator), cell adhesion (integrin-α2), and cell signaling (Rho B, cytosolic phospholipase A2), as well as a unique subset of cyclic pressure-sensitive genes such as vascular endothelial growth factor (VEGF)-C and transforming growth factor (TGF)-β2. The present study also provided first evidence that VEGF-C, the most highly induced gene under 60/20 mmHg, mediated HUVEC proliferation in response to this cyclic pressure. Cyclic pressure is, therefore, a mechanical force that modulates endothelial cell functions (such as proliferation) by activating a specific transcriptional program.

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