scholarly journals Nutrigenomic Effect of Hydroxytyrosol in Vascular Endothelial Cells: A Transcriptomic Profile Analysis

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3990
Author(s):  
Maria Annunziata Carluccio ◽  
Rosanna Martinelli ◽  
Marika Massaro ◽  
Nadia Calabriso ◽  
Egeria Scoditti ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Olive Oil ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Biological Properties ◽  
Functional Enrichment ◽  
Transcriptional Level ◽  
Protective Effects ◽  
New Genes ◽  
Canonical Pathways

Hydroxytyrosol (HT), a peculiar olive and olive oil phenolic antioxidant, plays a significant role in the endothelial and cardiovascular protection associated with olive oil consumption. However, studies examining the effects of HT on the whole-genome expression of endothelial cells, which are prominent targets for vasculo-protective effects of olive oil polyphenols, have been lacking. This study aims to comprehensively evaluate the genomic effects exerted by HT, at the transcriptional level, in endothelial cells under resting or proinflammatory conditions. Human umbilical vein endothelial cells (HUVECs) were treated with 10 µmol/L HT for 1 h and then stimulated with 5 ng/mL interleukin (IL)-1β for 3 h. Total RNA was extracted, and gene expression profile assessed with microarray analysis. Functional enrichment analysis and pathway analysis were performed by Ingenuity Pathways Analysis. Microarray data were validated by qRT-PCR. Fixing a significance threshold at 1.5-fold change, HT affected the expression of 708 and 599 genes, respectively, in HUVECs under resting and IL-1β-stimulated conditions; among these, 190 were common to both conditions. Unfolded protein response (UPR) and endoplasmic reticulum stress resulted from the two top canonical pathways common between HT and HT-IL-1β affected genes. IL-17F/A signaling was found in the top canonical pathways of HT modified genes under resting unstimulated conditions, whereas cardiac hypertrophy signaling was identified among the pathways affected by HT-IL-1β. The transcriptomic analysis allowed pinpointing immunological, inflammatory, proliferative, and metabolic-related pathways as the most affected by HT in endothelial cells. It also revealed previously unsuspected genes and related gene pathways affected by HT, thus broadening our knowledge of its biological properties. The unbiased identification of novel genes regulated by HT improves our understanding of mechanisms by which olive oil prevents or attenuates inflammatory diseases and identifies new genes to be enquired as potential contributors to the inter-individual variation in response to functional food consumption.

Panax Quinquefolium L. Inhibits Thrombin-Induced Endothelin Release In Vitro

1999 ◽  
Vol 27 (03n04) ◽  
pp. 331-338 ◽  
Author(s):  
Chun-Su Yuan ◽  
Anoja S. Attele ◽  
Ji An Wu ◽  
Tasha K. Lowell ◽  
Zhenlun Gu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Injury ◽  
Vascular Endothelial Cells ◽  
Cell Damage ◽  
Umbilical Vein ◽  
American Ginseng ◽  
Protective Effects ◽  
Panax Quinquefolium

Endothelial cell damage is considered to be the initial step in the genesis of thrombosis and arteriosclerosis, the common precursors of cardiovascular disorders. In this study, we evaluated the protective effects of American ginseng or Panax quinquefolium L. extracts on endothelial cell injury, and investigated effects of ginseng extracts on thrombin-induced endothelin release using cultured human umbilical vein endothelial cells. We observed that when endothelial cells pretreated with 1, 10, and 100 μg/ml of Panax quinquefolium L. extracts were incubated for 4 and 24 hr with thrombin, the concentration of endothelin was significantly decreased in a concentration dependent, time related manner (at 4 hr, IC50 = 5.1 μg/ml; at 24 hr, IC50 = 6.2 μg/ml). We further evaluated the effects of NG-nitro-L-arginine (NLA), a nitric oxide (NO) synthetase inhibitor, on the activity of Panax quinquefolium L. extracts. Following pretreatment of cultured endothelial cells with NLA, the inhibition of thrombin-induced endothelin release by Panax quinquefolium L. was significantly reduced (P < 0.05). This result suggests that the pharmacological action of Panax quinquefolium L. is, at least partially, due to NO release. Our data demonstrate that American ginseng may play a therapeutic role in facilitating the hemodynamic balance of vascular endothelial cells.

Anti-Inflammatory Effects ofDanshenon Human Vascular Endothelial Cells in Culture

2013 ◽  
Vol 41 (05) ◽  
pp. 1065-1077 ◽  
Author(s):  
Christian Stumpf ◽  
Quiaoling Fan ◽  
Christian Hintermann ◽  
Dorette Raaz ◽  
Ingrid Kurfürst ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecules ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Cellular Adhesion ◽  
Tanshinone Iia ◽  
Protective Effects ◽  
Induced Expression ◽  
Tnf Α ◽  
Anti Inflammatory

Inflammation plays a crucial role in the pathophysiology of atherosclerosis. Besides cytokines, chemokines and cell adhesion molecules, CD40 and P-selectin play important roles as key regulators of the inflammatory process in atherosclerosis. Danshen (DS) is commonly used in traditional Chinese medicine for therapy of cardiovascular diseases such as coronary artery disease. The aim of the present study was to evaluate the protective effects of DS with respect to possible anti-inflammatory effects. Human umbilical vein endothelial cells as well as platelets were incubated with an extract of DS or one of its major ingredients salvianolic acid B (Sal B), tanshinone IIA (Tansh) and protocatechuic acid (Protoc) under tumor necrosis factor (TNF)-α or ADP stimulation. Expression of CD40 and cellular adhesion molecules (VCAM-1/ICAM-1) were assessed via flow cytometry. Levels of interleukin (IL)-6, IL-8, monocyte-chemoattractant-protein (MCP)-1 as well as soluble VCAM1 and ICAM-1 in the supernatants were examined via luminex based analysis. Treatment with DS attenuated TNF-α induced expression of CD40. Furthermore, the expression of VCAM-1 and ICAM-1 as well as the release of soluble VCAM-1 and ICAM-1 were downregulated. In the cell supernatants we also observed a significant reduction of IL-6, IL8 and MCP-1. DS and its major ingredients, Sal B and Protoc, significantly inhibited TNF-induced expression and release of adhesion molecules, cytokines and chemokines as well as ADP-induced expression of platelet P-selectin. Because of the key roles of inflammatory mediators in the etiology of atherosclerosis, this work provides useful insight in understanding the pharmacological efficacy of Chinese herbal medicine.

scholarly journals Genistein Acutely Stimulates Nitric Oxide Synthesis in Vascular Endothelial Cells by a Cyclic Adenosine 5′-Monophosphate-Dependent Mechanism

Endocrinology ◽  
2004 ◽  
Vol 145 (12) ◽  
pp. 5532-5539 ◽  
Author(s):  
Dongmin Liu ◽  
Laurie L. Homan ◽  
Joseph S. Dillon
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Vascular Function ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Vascular Endothelial ◽  
Protective Effects ◽  
Nitric Oxide Synthesis ◽  
Enos Activity ◽  
Endothelial Nitric Oxide

Abstract Genistein may improve vascular function, but the mechanism of this effect is unclear. We tested the hypothesis that genistein directly regulates vascular function through stimulation of endothelial nitric oxide synthesis. Genistein activated endothelial nitric oxide synthase (eNOS) in intact bovine aortic endothelial cells and human umbilical vein endothelial cells over an incubation period of 10 min. The maximal eNOS activity was at 1 μm genistein. Consistent with this activation pattern, 1 μm genistein maximally stimulated the phosphorylation of eNOS at serine 1179 at 10 min of incubation. The rapid activation of eNOS by genistein was not dependent on RNA transcription or new protein synthesis and was not blocked by a specific estrogen receptor antagonist. In addition, inhibition of MAPK or phosphatidylinositol 3-OH kinase/Akt kinase had no affect on eNOS activation by genistein. Furthermore, the genistein effect on eNOS was also independent of tyrosine kinase inhibition. However, inhibition of cAMP-dependent kinase [protein kinase A (PKA)] by H89 completely abolished the genistein-stimulated eNOS activation and phosphorylation, suggesting that genistein acted through a PKA-dependent pathway. These findings demonstrated that genistein had direct nongenomic effects on eNOS activity in vascular endothelial cells, leading to eNOS activation and nitric oxide synthesis. These effects were mediated by PKA and were unrelated to an estrogenic effect. This cellular mechanism may underlie some of the cardiovascular protective effects proposed for soy phytoestrogens.

Modulation of Arachidonic Acid Metabolism in Human Endothelial Cells by Glucocorticoids

1986 ◽  
Vol 55 (03) ◽  
pp. 369-374 ◽  
Author(s):  
Raffaele De Caterina ◽  
Babette B Weksler
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Arachidonic Acid Metabolism ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor ◽  
Prolonged Incubation ◽  
Dependent Inhibition ◽  
Human Thrombin ◽  
Umbilical Vein Endothelial Cells

SummaryTo learn whether glucocorticoids inhibit prostaglandin (PG) production in vascular endothelial cells, we investigated the effects of glucocorticoids on PG synthesis by cultured human umbilical vein endothelial cells (EC). Pretreatment of EC with dexamethasone (DX, 10-9 to 5 x 10-5 M) caused a dose-dependent inhibition of PGI2 production when PG synthesis from endogenous arachidonate was stimulated by human thrombin (0.25-2 U/ml) or ionophore A 23187 (1-5 μM). The inhibition was detectable at 10-7 M DX and maximal at 10-5 M (4.0 ± 0.7 vs. control: 7.7 ± 1.9 ng/ml, mean ± S.D., P <0.01). The production of PGE2 and the release of radiolabelled arachidonate (AA) from prelabelled cells were similarly inhibited. Prolonged incubation of EC with glucocorticoids was required to inhibit PG production or arachidonate release: ranging from 8% inhibition at 5 h to 44% at 38 h. In contrast, prostaglandin formation from exogenous AA was not altered by DX treatment. When thrombin or ionophore-stimulated EC were restimulated with exogenous AA (25 μM), DX-treated cells released more PGI2 than control cells (5.7 ± 0.5 vs. 4.1 ± 0.6 ng/ml, P <0.01). Both the decrease in PGI2 production after thrombin/ionophore and the increase after re-stimulation with AA were blunted in the presence of the protein synthesis inhibitor cycloheximide (0.1-0.2 μg/ml). Thus, incubation of EC with glucocorticoids inhibits PG production at the step of phospholipase activation. The time requirement for these steroid effects and their blunting by cycloheximide are consistent with the induction of regulatory proteins, possibly lipocortins, in endothelial cells.

scholarly journals Ethanol inhibits monocyte chemotactic protein-1 expression in interleukin-1β-activated human endothelial cells

2005 ◽  
Vol 289 (4) ◽  
pp. H1669-H1675 ◽  
Author(s):  
John P. Cullen ◽  
Shariq Sayeed ◽  
Ying Jin ◽  
Nicholas G. Theodorakis ◽  
James V. Sitzmann ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Binding Activity ◽  
Protective Effects ◽  
Monocyte Adhesion ◽  
Monocyte Chemotactic Protein ◽  
Chemotactic Protein ◽  
Subendothelial Space ◽  
Umbilical Vein Endothelial Cells

The aim of this study was to determine the effect of ethanol (EtOH) on endothelial monocyte chemotactic protein-1 (MCP-1) expression. IL-1β increased the production of MCP-1 by human umbilical vein endothelial cells from undetectable levels to ∼900 pg/ml at 24 h. EtOH dose-dependently inhibited IL-1β-stimulated MCP-1 secretion as determined by ELISA: 25 ± 1%, 35 ± 7%, and 65 ± 5% inhibition for 1, 10, and 100 mM EtOH, respectively, concomitant with inhibition of monocyte adhesion to activated endothelial cells. Similarly, EtOH dose-dependently inhibited IL-1β-stimulated MCP-1 mRNA expression. Experiments with actinomycin D demonstrated that EtOH decreased the stability of MCP-1 mRNA. In addition, EtOH significantly reduced NF-κB and AP-1 binding activity induced by IL-1β and inhibited MCP-1 gene transcription. Binding of 125I-labeled MCP-1 to its receptor (CCR2) on THP-1 human monocytic cells was not affected by EtOH treatment. Modulation of the expression of MCP-1 represents a mechanism whereby EtOH could inhibit atherogenesis by blocking the crucial early step of monocyte adhesion and subsequent recruitment to the subendothelial space. These actions of EtOH may underlie, in part, its cardiovascular protective effects in vivo.

Stimulation of Tetrahydrobiopterin Synthesis by 17β-Estradiol in Brain Microvascular Endothelial Cells

Pteridines ◽  
2000 ◽  
Vol 11 (4) ◽  
pp. 129-132
Author(s):  
Kazuhiro Shiota ◽  
Masakazu Ishii ◽  
Toshinori Yamamoto ◽  
Shunichi Shimizu ◽  
Yuji Kiuchi
Keyword(s):  
Endothelial Cells ◽  
De Novo ◽  
Vascular Endothelial Cells ◽  
Mrna Level ◽  
Microvascular Endothelial Cells ◽  
No Production ◽  
Brain Microvascular Endothelial Cells ◽  
Protective Effects ◽  
17Β Estradiol ◽  
Microvascular Endothelial

Abstract The purpose of this study was to examine whether 17β-estradiol stimulates the synthesis of tetrahydrobiopterin : BH4), which is one of the cofactors of nitric oxide (NO) synthase, in mouse brain microvascular endothelial cells. Addition of 17()-estradiol to endothelial cells time- and concentration-dependently increased intracellular BH4 level. 17β-Estradiol also stimulated the mRNA level of GTP-cyclohydrolase I (GTPCH), which is a rate-limiting enzyme of the de novo BH4 synthetic pathway. In addition, the 17β-estradiol-induced expression of GTPCH mRNA was strongly attenuated by treatment with an inhibitor of 17β-estradiol receptor 4-hydroxy-tamoxlfen. These results suggest that 17β-estradiol stimulates BH4 synthesis through the induction of GTPCH by tamoxifensensitive receptor in vascular endothelial cells. The 17β-estradiol-induced increase in BH4 level might be implicated in not only NO production, but also protective effects of 17β-estradiol against ischemic brain damage and atherosclerosis, since BH4 is an intracellular antioxidant.

scholarly journals Protein C system defects inflicted by the malaria parasite protein PfEMP1 can be overcome by a soluble EPCR variant

2015 ◽  
Vol 114 (11) ◽  
pp. 1038-1048 ◽  
Author(s):  
Eveline A. M. Bouwens ◽  
Ibai Tamayo ◽  
Louise Turner ◽  
Christian W. Wang ◽  
Monique Stins ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Severe Malaria ◽  
Protein C ◽  
Cellular Response ◽  
Malaria Parasite ◽  
Vascular Endothelial Cells ◽  
Protective Effects ◽  
Endothelial Protein C Receptor ◽  
Parasite Protein ◽  
Soluble Epcr

SummaryThe Endothelial Protein C receptor (EPCR) is essential for the anticoagulant and cytoprotective functions of the Protein C (PC) system. Selected variants of the malaria parasite protein, Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) associated with severe malaria, including cerebral malaria, specifically target EPCR on vascular endothelial cells. Here, we examine the cellular response to PfEMP1 engagement to elucidate its role in malaria pathogenesis. Binding of the CIDRα1.1 domain of PfEMP1 to EPCR obstructed activated PC (APC) binding to EPCR and induced a loss of cellular EPCR functions. CIDRα1.1 severely impaired endothelial PC activation and effectively blocked APC-mediated activation of protease-activated receptor-1 (PAR1) and associated barrier protective effects of APC on endothelial cells. A soluble EPCR variant (E86A-sEPCR) bound CIDRα1.1 with high affinity and did not interfere with (A)PC binding to cellular EPCR. E86A-sEPCR used as a decoy to capture PfEMP1, permitted normal PC activation on endothelial cells, normal barrier protective effects of APC, and greatly reduced cytoadhesion of infected erythrocytes to brain endothelial cells. These data imply important contributions of PfEMP1-induced protein C pathway defects in the pathogenesis of severe malaria. Furthermore, the E86A-sEPCR decoy provides a proof-of-principle strategy for the development of novel adjunct therapies for severe malaria.

scholarly journals Total flavonoids from Astragalus alleviate endothelial dysfunction by activating the Akt/eNOS pathway

2017 ◽  
Vol 46 (6) ◽  
pp. 2096-2103 ◽  
Author(s):  
Qian Liu ◽  
Ling Zhang ◽  
Qiyuan Shan ◽  
Yuxia Ding ◽  
Zhaocai Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Vascular Endothelial Cells ◽  
Ex Vivo ◽  
Umbilical Vein ◽  
Cell Counting ◽  
Total Flavonoids ◽  
Vascular Endothelial ◽  
Protective Effects ◽  
Hypoxic Conditions ◽  
Underlying Mechanisms

Objective To investigate the vasodilative and endothelial-protective effects and the underlying mechanisms of total flavonoids from Astragalus (TFA). Methods The vasodilative activities of TFA were measured with a myograph ex vivo using rat superior mesenteric arterial rings. The primary human umbilical vein endothelial cell (HUVEC) viabilities were assayed using the cell counting kit-8 after hypoxia or normoxia treatment with or without TFA. Akt, P-Akt, eNOS, P-eNOS, Erk, P-Erk, Bcl-2 and Bax expression were analyzed using western blotting. Results TFA showed concentration-dependent vasodilative effects on rat superior mesenteric arterial rings, but had no effects on normal or potassium chloride precontracted arterial rings. TFA did not affect HUVEC viabilities in normoxia, but dramatically promoted cell proliferation in the concentration range of 1 to 30 µg/mL under hypoxia. Moreover, TFA significantly increased the ratios of P-Akt/Akt and P-eNOS/eNOS in vascular endothelial cells under hypoxic conditions, but did not change the P-Erk/Erk or Bcl-2/Bax ratios. Conclusions TFA might exhibit vasorelaxant and endothelial-protective effects via the Akt/eNOS signaling pathway.

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