Vascular Protective Effects of Xanthotoxin and Its Action Mechanism in Rat Aorta and Human Vascular Endothelial Cells

2020 ◽  
Vol 57 (6) ◽  
pp. 313-324
Author(s):  
Li-Hua Cao ◽  
Ho Sub Lee ◽  
Zhe-Shan Quan ◽  
Yun Jung Lee ◽  
Yu Jin
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Neuroprotective Effect ◽  
Intercellular Adhesion Molecule ◽  
Dependent Manner ◽  
Protective Effects ◽  
Concentration Dependent Manner

<b><i>Objective:</i></b> Xanthotoxin (XAT) is a linear furanocoumarin mainly extracted from the plants <i>Ammi majus</i> L. XAT has been reported the apoptosis of tumor cells, anti-convulsant, neuroprotective effect, antioxidative activity, and vasorelaxant effects. This study aimed to investigate the vascular protective effects and underlying molecular mechanisms of XAT. <b><i>Methods:</i></b> XAT’s activity was studied in rat thoracic aortas, isolated with aortic rings, and human umbilical vein endothelial cells (HUVECs). <b><i>Results:</i></b> XAT induced endothelium-dependent vasodilation in a concentration-dependent manner in the isolated rat thoracic aortas. Removal of endothelium or pretreatment of aortic rings with L-NAME, 1<i>H</i>-[1,2,4]-oxadiazolo-[4,3-<i>a</i>]-quinoxalin-1-one, and wortmannin significantly inhibited XAT-induced relaxation. In addition, treatment with thapsigargin, 2-aminoethyl diphenylborinate, Gd<sup>3+</sup>, and 4-aminopyridine markedly attenuated the XAT-induced vasorelaxation. XAT increased nitric oxide production and Akt- endothelial NOS (eNOS) phosphorylation in HUVECs. Moreover, XAT attenuated the expression of TNF-α-induced cell adhesion molecules such as intercellular adhesion molecule, vascular cell adhesion molecule-1, and E-selectin. However, this effect was attenuated by the eNOS inhibitors L-NAME and asymmetric dimethylarginine. <b><i>Conclusions:</i></b> This study suggests that XAT induces vasorelaxation through the Akt-eNOS-cGMP pathway by activating the K<sub>V</sub> channel and inhibiting the L-type Ca<sup>2+</sup> channel. Furthermore, XAT exerts an inhibitory effect on vascular inflammation, which is correlated with the observed vascular protective effects.

Ligation of CD31 (PECAM-1) on Endothelial Cells Increases Adhesive Function of vβ3 Integrin and Enhances β1 Integrin-Mediated Adhesion of Eosinophils to Endothelial Cells

Blood ◽  
1999 ◽  
Vol 94 (4) ◽  
pp. 1319-1329 ◽  
Author(s):  
Ryuichi Chiba ◽  
Noriaki Nakagawa ◽  
Kazuhiro Kurasawa ◽  
Yoshiya Tanaka ◽  
Yasushi Saito ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Umbilical Vein ◽  
Rgd Peptide ◽  
Interleukin 4 ◽  
Intercellular Adhesion Molecule ◽  
Β1 Integrin ◽  
Lymphocyte Function ◽  
Dependent Manner ◽  
Stimulation Of

Abstract We determined the role of the heterophilic interaction of vβ3 integrin on endothelial cells with CD31 on leukocytes in mediating leukocyte-endothelial cell interactions. Preincubation of interleukin-4 (IL-4)–stimulated human umbilical vein endothelial cells (HUVECs) with anti-CD31 monoclonal antibodies (MoAbs) enhanced eosinophil adhesion to the IL-4–stimulated HUVECs, and the endothelial CD31-induced enhancement of eosinophil adhesion to IL-4–stimulated HUVECs was prevented by anti–vascular cell adhesion molecule-1 (VCAM-1) MoAb and anti–very late activation antigen-4 (VLA-4) MoAb, but not by anti–intercellular adhesion molecule-1 (ICAM-1) MoAb, anti–lymphocyte function-associated antigen-1 (LFA-1) MoAb, anti–P-selectin MoAb, or anti–E-selectin MoAb. CD31 stimulation of HUVECs increased the adhesive function of vβ3 integrin to its ligand RGD peptide, the binding of which reached a maximum at 10 minutes after the stimulation, and the CD31-induced vβ3 integrin activation on HUVECs was inhibited by inhibitors of protein kinase C and phosphatidylinositol 3 kinase (PI3-kinase). Furthermore, anti-vβ3 integrin MoAb and RGD peptide as well as soluble CD31 inhibited endothelial CD31-induced enhancement of eosinophil adhesion to IL-4–stimulated HUVECs. However, anti-vβ3 integrin MoAb had no significant inhibitory effect on the eosinophil adhesion to IL-4–stimulated or unstimulated HUVECs without CD31 stimulation of HUVECs. Finally, CD31 stimulation of eosinophils increased the adhesive function of 4β1 integrin (VLA-4) to its ligand fibronectin and their adhesion to IL-4–stimulated HUVECs in a VLA-4–dependent manner. These results indicate that CD31-mediated inside-out signaling activates vβ3 integrin on endothelial cells, that the heterophilic vβ3 integrin/CD31 interaction induces β1 integrin-mediated adhesion of eosinophils to endothelial cells, and that the heterophilic interaction itself is not significantly involved in firm adhesion of eosinophils to endothelial cells.

Ligation of CD31 (PECAM-1) on Endothelial Cells Increases Adhesive Function of vβ3 Integrin and Enhances β1 Integrin-Mediated Adhesion of Eosinophils to Endothelial Cells

Blood ◽  
1999 ◽  
Vol 94 (4) ◽  
pp. 1319-1329 ◽  
Author(s):  
Ryuichi Chiba ◽  
Noriaki Nakagawa ◽  
Kazuhiro Kurasawa ◽  
Yoshiya Tanaka ◽  
Yasushi Saito ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Umbilical Vein ◽  
Rgd Peptide ◽  
Interleukin 4 ◽  
Intercellular Adhesion Molecule ◽  
Β1 Integrin ◽  
Lymphocyte Function ◽  
Dependent Manner ◽  
Stimulation Of

We determined the role of the heterophilic interaction of vβ3 integrin on endothelial cells with CD31 on leukocytes in mediating leukocyte-endothelial cell interactions. Preincubation of interleukin-4 (IL-4)–stimulated human umbilical vein endothelial cells (HUVECs) with anti-CD31 monoclonal antibodies (MoAbs) enhanced eosinophil adhesion to the IL-4–stimulated HUVECs, and the endothelial CD31-induced enhancement of eosinophil adhesion to IL-4–stimulated HUVECs was prevented by anti–vascular cell adhesion molecule-1 (VCAM-1) MoAb and anti–very late activation antigen-4 (VLA-4) MoAb, but not by anti–intercellular adhesion molecule-1 (ICAM-1) MoAb, anti–lymphocyte function-associated antigen-1 (LFA-1) MoAb, anti–P-selectin MoAb, or anti–E-selectin MoAb. CD31 stimulation of HUVECs increased the adhesive function of vβ3 integrin to its ligand RGD peptide, the binding of which reached a maximum at 10 minutes after the stimulation, and the CD31-induced vβ3 integrin activation on HUVECs was inhibited by inhibitors of protein kinase C and phosphatidylinositol 3 kinase (PI3-kinase). Furthermore, anti-vβ3 integrin MoAb and RGD peptide as well as soluble CD31 inhibited endothelial CD31-induced enhancement of eosinophil adhesion to IL-4–stimulated HUVECs. However, anti-vβ3 integrin MoAb had no significant inhibitory effect on the eosinophil adhesion to IL-4–stimulated or unstimulated HUVECs without CD31 stimulation of HUVECs. Finally, CD31 stimulation of eosinophils increased the adhesive function of 4β1 integrin (VLA-4) to its ligand fibronectin and their adhesion to IL-4–stimulated HUVECs in a VLA-4–dependent manner. These results indicate that CD31-mediated inside-out signaling activates vβ3 integrin on endothelial cells, that the heterophilic vβ3 integrin/CD31 interaction induces β1 integrin-mediated adhesion of eosinophils to endothelial cells, and that the heterophilic interaction itself is not significantly involved in firm adhesion of eosinophils to endothelial cells.

scholarly journals Monocytic microparticles activate endothelial cells in an IL-1β–dependent manner

Blood ◽  
2011 ◽  
Vol 118 (8) ◽  
pp. 2366-2374 ◽  
Author(s):  
Jian-Guo Wang ◽  
Julie C. Williams ◽  
Beckley K. Davis ◽  
Ken Jacobson ◽  
Claire M. Doerschuk ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecules ◽  
Bacterial Infections ◽  
Mononuclear Cells ◽  
Intercellular Adhesion Molecule ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear

Abstract Microparticles (MPs) are shed from activated and dying cells. They can transmit signals from cell to cell, locally or at a distance through the circulation. Monocytic MPs are elevated in different diseases, including bacterial infections. Here, we investigated how monocytic MPs activate endothelial cells. We found that MPs from lipopolysaccharide (LPS)–treated THP-1 monocytic cells bind to and are internalized by human endothelial cells. MPs from LPS-treated THP-1 cells, but not untreated cells, induced phosphorylation of ERK1/2, activation of the nuclear factor-κB pathway and expression of cell adhesion molecules intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin. Similar results were observed using MPs from LPS-treated peripheral blood mononuclear cells. We next investigated the mechanism by which monocytic MPs activated endothelial cells and found that they contain IL-1β and components of the inflammasome, including apoptosis-associated speck-like protein containing a CARD, caspase-1, and NLRP3. Importantly, knockdown of NLRP3 in THP-1 cells reduced the activity of the MPs and blockade of the IL-1 receptor on endothelial cells decreased MP-dependent induction of cell adhesion molecules. Therefore, monocytic MPs contain IL-1β and may amplify inflammation by enhancing the activation of the endothelium.

scholarly journals Effect of selective proteasome inhibitors on TNF-induced activation of primary and transformed endothelial cells

1999 ◽  
Vol 276 (4) ◽  
pp. C856-C864 ◽  
Author(s):  
Theodore J. Kalogeris ◽  
F. Stephen Laroux ◽  
Adam Cockrell ◽  
Hiroshi Ichikawa ◽  
Naotsuka Okayama ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Leukocyte Adhesion ◽  
Umbilical Vein ◽  
Proteasome Inhibitors ◽  
26S Proteasome ◽  
Polymorphonuclear Neutrophil ◽  
Intercellular Adhesion Molecule

The objective of this study was to assess the effects of two structurally distinct yet selective proteasome inhibitors (PS-341 and lactacystin) on leukocyte adhesion, endothelial cell adhesion molecule (ECAM) expression, and nuclear factor-κB (NF-κB) activation in tumor necrosis factor (TNF)-α-stimulated human umbilical vein endothelial cells (HUVEC) and the transformed, HUVEC-derived, ECV cell line. We found that TNF (10 ng/ml) significantly enhanced U-937 and polymorphonuclear neutrophil (PMN) adhesion to HUVEC but not to ECV; TNF also significantly enhanced surface expression of vascular cell adhesion molecule 1 and E-selectin (in HUVEC only), as well as intercellular adhesion molecule 1 (ICAM-1; in HUVEC and ECV). Pretreatment of HUVEC with lactacystin completely blocked TNF-stimulated PMN adhesion, partially blocked U-937 adhesion, and completely blocked TNF-stimulated ECAM expression. Lactacystin attenuated TNF-stimulated ICAM-1 expression in ECV. Pretreatment of HUVEC with PS-341 partially blocked TNF-stimulated leukocyte adhesion and ECAM expression. These effects of lactacystin and PS-341 were associated with inhibitory effects on TNF-stimulated NF-κB activation in both HUVEC and ECV. Our results demonstrate the importance of the 26S proteasome in TNF-induced activation of NF-κB, ECAM expression, and leukocyte-endothelial adhesive interactions in vitro.

scholarly journals HMC05, Herbal Formula, Inhibits TNF-α-Induced Inflammatory Response in Human Umbilical Vein Endothelial Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Jong Suk Lee ◽  
Su-Young Park ◽  
Dinesh Thapa ◽  
Ah Ra Kim ◽  
Heung-Mook Shin ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Umbilical Vein ◽  
Vascular Inflammation ◽  
Lipid Lowering ◽  
Dependent Manner ◽  
Herbal Formula ◽  
Cell Adhesion Molecule 1

Vascular inflammation has been implicated in the progression of cardiovascular diseases such as atherosclerosis. In the present study, we found that HMC05, an extract from eight different herbal mixtures, dose-dependently inhibited tumor necrosis factor-α(TNF-α)-induced adhesion of monocytes to endothelial cells. Such inhibitory effect of HMC05 correlated with suppressed expression of monocyte chemoattractant protein-1, CC chemokine receptor 2, vascular cell adhesion molecule-1 and intercellular cell adhesion molecule-1. In addition, HMC05 significantly inhibited production of reactive oxygen species (ROS) and nuclear factor (NF)-κB activation by TNF-α. Those inhibitory effects of HMC05 (1–10 μg mL−1) on the TNF-α-induced inflammatory event was similar to those of berberine (1–10 μM), which is a major component of HMC05 and one of herbal compounds known to have vasorelaxing and lipid-lowering activities. However, berberine significantly reduced the viability of HUVECs in a time- and concentration-dependent manner. In contrast, HMC05 (1–10 μg ml−1) did not affect the cell viability for up to 48 h treatment. In conclusion, we propose that HMC05 may be a safe and potent herbal formula against vascular inflammation, and its action may be attributable to the inhibition of ROS- and NF-κB-dependent expression of adhesion molecules and chemokines.

scholarly journals Adhesion of human basophils, eosinophils, and neutrophils to interleukin 1-activated human vascular endothelial cells: contributions of endothelial cell adhesion molecules.

1991 ◽  
Vol 173 (6) ◽  
pp. 1553-1557 ◽  
Author(s):  
B S Bochner ◽  
F W Luscinskas ◽  
M A Gimbrone ◽  
W Newman ◽  
S A Sterbinsky ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Endothelial Cell ◽  
Adhesion Molecule ◽  
Umbilical Vein ◽  
Interleukin 1 ◽  
Intercellular Adhesion Molecule ◽  
Neutrophil Adhesion ◽  
Cell Type ◽  
Human Basophils

Cytokines such as interleukin 1 (IL-1) promote adhesiveness in human umbilical vein endothelial cells for leukocytes including basophils, eosinophils, and neutrophils, and induce expression of adherence molecules including ICAM-1 (intercellular adhesion molecule-1), ELAM-1 (endothelial-leukocyte adhesion molecule-1), and VCAM-1 (vascular cell adhesion molecule-1). In the present study, blocking monoclonal antibodies (mAb) recognizing ICAM-1, ELAM-1, and VCAM-1 have been used to compare their roles in IL-1-induced adhesion of human basophils, eosinophils, and neutrophils. IL-1 treatment of endothelial cell monolayers for 4 hours induced a four- to eight-fold increase in adhesion for each cell type. Treatment of endothelial cells with either anti-ICAM-1 or anti-ELAM-1 mAb inhibited IL-1-induced adherence of each cell type. In contrast, treatment with anti-VCAM-1 mAb inhibited basophil and eosinophil (but not neutrophil) adhesion, and was especially effective in blocking eosinophil adhesion. The effects of these mAb were at least additive. Indirect immunofluorescence and flow cytometry demonstrated expression of VLA-4 alpha (very late activation antigen-4 alpha, a counter-receptor for VCAM-1) on eosinophils and basophils but not on neutrophils. These data document distinct roles for ICAM-1, ELAM-1, and VCAM-1 during basophil, eosinophil, and neutrophil adhesion in vitro, and suggest a novel mechanism for the recruitment of eosinophils and basophils to sites of inflammation in vivo.

scholarly journals Fimbria-Dependent Activation of Cell Adhesion Molecule Expression in Porphyromonas gingivalis-Infected Endothelial Cells

2002 ◽  
Vol 70 (1) ◽  
pp. 257-267 ◽  
Author(s):  
Mary Khlgatian ◽  
Hamdy Nassar ◽  
Hsin-Hua Chou ◽  
Frank C. Gibson ◽  
Caroline Attardo Genco
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Porphyromonas Gingivalis ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Inflammatory Diseases ◽  
Umbilical Vein ◽  
Intercellular Adhesion Molecule ◽  
Adhesion Molecule Expression

ABSTRACT Porphyromonas gingivalis is an oral pathogen that has recently been associated with chronic inflammatory diseases such as atherosclerosis. The strength of the epidemiological associations of P. gingivalis with atherosclerosis can be increased by the demonstration that P. gingivalis can initiate and sustain growth in human vascular cells. We previously established that P. gingivalis can invade aortic, heart, and human umbilical vein endothelial cells (HUVEC), that fimbriae are required for invasion of endothelial cells, and that fimbrillin peptides can induce the expression of the chemokines interleukin 8 and monocyte chemotactic protein. In this study, we examined the expression of surface-associated cell adhesion molecules on endothelial cells in response to P. gingivalis infection by fluorescence-activated cell sorting FACS analysis and confocal microscopy. Coculture of HUVEC with P. gingivalis strain 381 or A7436 resulted in the induction in the expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and P- and E-selectins, which was maximal at 48 h postinfection. In contrast, we did not observe induction of ICAM-1, VCAM-1, or P- or E-selectin expression in HUVEC cultured with the noninvasive P. gingivalis fimA mutant DPG3 or when P. gingivalis was incubated with fimbrillin peptide-specific anti-sera prior to the addition to HUVEC. Furthermore, the addition of a peptide corresponding to the N-terminal domain of fimbrillin to HUVEC resulted in an increase in ICAM-1, VCAM-1, and P- and E-selectins, which was maximal at 48 h and similar to that observed for live P. gingivalis. Treatment of P. gingivalis-infected HUVEC with cytochalsin D, which prevented P. gingivalis invasion, also resulted in the inhibition of ICAM-1, VCAM-1, or P- and E-selectin expression. Taken together, these results indicate that active P. gingivalis invasion of HUVEC mediated via the major fimbriae stimulates surface-associated cell adhesion molecule expression. Stimulation of adhesion molecules involved in the recruitment of leukocytes to sites of inflammation by P. gingivalis may play a role in the pathogenesis of systemic inflammatory diseases associated with this microorganism, including atherosclerosis.

Cyclic strain and motion control produce opposite oxidative responses in two human endothelial cell types

2007 ◽  
Vol 293 (1) ◽  
pp. C87-C94 ◽  
Author(s):  
Hak-Joon Sung ◽  
Andrew Yee ◽  
Suzanne G. Eskin ◽  
Larry V. McIntire
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Protein Expression ◽  
Motion Control ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Umbilical Vein ◽  
Cyclic Strain ◽  
Intercellular Adhesion Molecule ◽  
Static Conditions

The phenotype of endothelial cells (ECs) is specific to the vascular bed from which they originate. To examine how mechanical forces alter the phenotype of different ECs, we compared the effects of cyclic strain and motion control on reactive oxygen species (ROS) production and metabolism and cell adhesion molecule expression in human umbilical vein endothelial cells (HUVEC) vs. human aortic endothelial cells (HAEC). HUVEC and HAEC were subjected to cyclic strain (10% or 20%, 1 Hz), to a motion control that simulated fluid agitation over the cells without strain, or to static conditions for 24 h. We measured H2O2production with dichlorodihydrofluorescein acetate and superoxide with dihydroethidium fluorescence changes; superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) activities spectrophotometrically; and vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 protein expression with Western blot analyses. HUVEC under cyclic strain showed 1) higher intracellular H2O2levels, 2) increased SOD, catalase, and GPx activities, and 3) greater VCAM-1 and ICAM-1 protein expression, compared with motion control or static conditions. However, in HAEC, motion control induced higher levels of ROS, enzyme activities associated with ROS defense, and VCAM-1 and ICAM-1 expression than cyclic strain. The opposite responses obtained with these two human EC types may reflect their vessels of origin, in that HAEC are subjected to higher cyclic strain deformations in vivo than HUVEC.

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