scholarly journals A comparison of the effects of monotherapy with rosuvastatin, atorvastatin or ezetimibe versus combination treatment with rosuvastatin-ezetimibe and atorvastatin-ezetimibe on the integrity of vascular endothelial cells damaged by oxidized cholesterol

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0256996
Author(s):  
Mateusz Niedzielski ◽  
Marlena Broncel ◽  
Paulina Gorzelak-Pabiś ◽  
Ewelina Woźniak
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Mrna Level ◽  
Control Group ◽  
Vascular Endothelial ◽  
Cell Integrity ◽  
Protein Levels ◽  
Oxidized Cholesterol ◽  
Intercellular Adhesion Molecules ◽  
Endothelial Integrity

Dyslipidemia, atherosclerosis, and cardiovascular events can be prevented, or treated, using statins, alone or in combination with ezetimibe. The aim of the study was to compare the direct pleiotropic effects of two commonly-used statins (atorvastatin, rosuvastatin), ezetimibe and their combinations on endothelial cells damaged by oxidized cholesterol. HUVEC cultures were stimulated for 20 hours with atorvastatin (5 μM; 2793 ng/mL), rosuvastatin (10 μM; 4815 ng/mL), ezetimibe (1.22 μM; 500 ng/mL), atorvastatin plus ezetimibe (5 μM + 1.22 μM; 2793 ng/mL + 500 ng/mL) and rosuvastatin plus ezetimibe (10 μM + 1.22 μM; 4815 ng/mL + 500ng/mL) in separate groups, with or without 25-hydroxycholesterol pre-incubation (24.83 μM; 10 μg/mL; four hours then washout). HUVEC integrity was measured in the RTCA-DP xCELLigence system. The mRNA expression and protein levels of ZO-1, OCLN, ICAM-1 were analyzed by real-time PCR and ELISA. Pre-incubation with 25-OHC resulted in decreased endothelial cell integrity (p<0.001), decreased expression of ZO-1 mRNA (p<0.05) and protein levels (p<0.05), OCLN mRNA (p<0.05) and protein levels (p<0.05) and increased ICAM-1 mRNA (p<0.001) and protein levels (p<0.001) compared to the control group. Incubation with rosuvastatin (12h p<0.01; 24h p<0.001) and atorvastatin (only 12h p<0.05) restored HUVEC integrity. Subsequent incubation with rosuvastatin increased ZO-1 mRNA (p<0.001) and protein (p<0.001) levels. Subsequent addition of ezetimibe increased ZO-1 mRNA level (p<0.001) but not protein level. Furthermore, only incubation with rosuvastatin increased OCLN mRNA (p<0.05) and protein (p<0.05) levels. In each drug-stimulated group, both ICAM-1 mRNA and protein levels were reduced after initial incubation with oxysterol (p<0.05). 25-hydroxycholesterol disrupts endothelial integrity, decreases the mRNA and protein levels of tight junction, and increases those of intercellular adhesion molecules. Both rosuvastatin and atorvastatin can improve endothelial integrity, but only rosuvastatin can completely abolish the effect of oxysterol. The combination of statins with ezetimibe has less direct effect on the endothelial barrier than the statins alone.

The regulation and mechanism of a dual PI3K/mTOR signaling inhibitor in hemangioma vascular endothelial cells in vitro

2020 ◽  
Author(s):  
wangshu liu ◽  
Yang Yu ◽  
Juan Li ◽  
Hui Huang ◽  
Hao Liu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Signaling Pathway ◽  
Vascular Endothelial Cells ◽  
Mtor Signaling ◽  
Control Group ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Mtor Signaling Pathway ◽  
Protein Levels

Abstract Objective To observe the influence of the dual PI3K/mTOR inhibitor NVP-BEZ235 on proliferation and apoptosis of hemangioma cells in vitro and key molecules of the PI3K/Akt/mTOR signaling pathway.Methods Hemangioma-derived endothelial cells (HeECs) were obtained by surgical resection and cultured after the explants with the trypsin-digestion method. Fourth generation cells were cultured with serum-free medium for 24 hours. Then, the intervention group cells were added to the culture medium with 0.50 μM or 1.00 μM NVP-BEZ235. Cell proliferation was detected with CCK-8 assays, apoptosis was detected by flow cytometry, and PI3K, Akt, mTOR, and p70s6k protein levels were detected by Western blots. Then, the relationship between the phenotype of hemangioma vascular endothelial cells and the four proteins was analyzed.Results the 0.50 μM and 1.00 μM NVP-BEZ235 groups were significantly lower (0.88±0.03 and 0.59±0.05, respectively) than the control group (1.10±0.02) (P<0.01). The rate of G0/G1 phase cells in the 0.50 μM and 1.00 μM NVP-BEZ235 group were higher than the control group (P<0.01). The total rates of apoptotic cells in the 0.50 μM and 1.00 μM NVP-BEZ235 groups were higher than the control group (2.77±1.23)% (P<0.01). The PI3K pathway related protein levels in the NVP-BEZ235 group were lower than control group (P<0.01).Conclusion The PI3K/Akt/mTOR signaling pathway participates in hemangioma development. NVP-BEZ235 affected hemangioma vascular endothelial cells in vitro by regulating the PI3K/Akt/mTOR signaling pathway in a dose-dependent manner.

scholarly journals The Use of Fiber-Reinforced Scaffolds Cocultured with Schwann Cells and Vascular Endothelial Cells to Repair Rabbit Sciatic Nerve Defect with Vascularization

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Hongyang Gao ◽  
Yang You ◽  
Guoping Zhang ◽  
Feng Zhao ◽  
Ziyi Sha ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Sciatic Nerve ◽  
Nerve Fiber ◽  
Schwann Cells ◽  
Vascular Endothelial Cells ◽  
Neurological Function ◽  
Control Group ◽  
Vascular Endothelial ◽  
Fiber Reinforced ◽  
3D Scaffolds

To explore the feasibility of biodegradable fiber-reinforced 3D scaffolds with satisfactory mechanical properties for the repair of long-distance sciatic nerve defect in rabbits and effects of vascularized graft in early stage on the recovery of neurological function, Schwann cells and vascular endothelial cells were cocultured in the fiber-reinforced 3D scaffolds. Experiment group which used prevascularized nerve complex for the repair of sciatic nerve defect and control group which only cultured with Schwann cells were set. The animals in both groups underwent electromyography to show the status of the neurological function recovery at 4, 8, and 16 weeks after the surgery. Sciatic nerve regeneration and myelination were observed under the light microscope and electron microscope. Myelin sheath thickness, axonal diameter, and number of myelinated nerve fiber were quantitatively analyzed using image analysis system. The recovery of foot ulcer, the velocity of nerve conduction, the number of regenerating nerve fiber, and the recovery of ultrastructure were increased in the experimental group than those in the control group. Prevascularized tissue engineered fiber-reinforced 3D scaffolds for the repair of sciatic nerve defects in rabbits can effectively promote the recovery of neurological function.

Abstract 5456: Vascular Endothelial Cells Endothelin-1 Deficiency Decreased Vascular Protection in Atherosclerosis Mouse Model

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Dyah Wulan Anggrahini ◽  
Noriaki Emoto ◽  
Kazuhiko Nakayama ◽  
Bambang Widyantoro ◽  
Kazuya Miyagawa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Vessel Wall ◽  
Vascular Endothelial Cells ◽  
Mrna Level ◽  
Vascular Wall ◽  
Protective Mechanism ◽  
Vascular Endothelial ◽  
Vascular Protection ◽  
Plaque Instability

Endothelium plays important role in protective mechanism of vascular wall. The balance between endothelin-1 (ET-1) and nitric oxide provide endothelial barrier to lipoprotein retain and macrophage recruitment. In contrasts, ET-1 is also a strong vasoconstrictor. In this study, we aim to determine the role of vascular endothelial cells-derived ET-1 in the development of atherosclerosis. For that purpose, we crossbred Vascular Endothelial Cells-specific ET-1 Knockout (VEETKO) mice to ApoEKO mice. ApoE/VEET-DKO exhibited significantly lower ET-1 plasma and mRNA level as compared to ApoEKO mice. No significant differences of blood pressure, plasma cholesterol or lipid profiles were observed in both mice. Surprisingly, after 8 weeks of western diet, we found that the atherosclerotic lesion was exaggerated in the aortic sinus and brachiochepalic artery of ApoE/VEET-DKO mice (n=7) as compared to those of ApoEKO mice (n=7) (ratio/vessel wall, 0.93±0.13vs.0.49±0.09, p<0.05). We further showed the increase in macrophage plaque content and peritoneal macrophage recruitment in DKO mice. To understand the mechanism of vascular protection, we found lower eNOS mRNA level in DKO mice despite only lower tendency of ETB receptor expression. Functionally, the mice lacking ET-1 in endothelial cells showed impaired NO-mediated endothelial function. Decreased vascular protection further led to increase plaque instability in DKO mice. Here we showed that plaque of DKO mice was more lipid enrich as compared to that of ApoEKO (ratio/lesion, 0.56±0.03vs.0.42±0.04, p<0.05). Moreover, lack of ET-1 significantly reduced matrix synthesis following lower SMCs accumulation in the lesion (ratio/vessel wall, 0.28±0.06vs.0.57±0.08, p<0.05), which was mediated by TGFβ. Interestingly, despite similar advance-typed lesion formed, 15% of DKO mice exhibited plaque hemorrhage in brachiochepalic artery. In conclusion, we demonstrated the increase in atherosclerosis and plaque instability in our model. This further suggests that ET-1 produced from vascular endothelial cells is required for protective mechanism in vascular wall in balance with nitric oxide production. Our data imply for the careful monitoring in the use of ET receptor antagonist in clinical setting.

scholarly journals Protective Effects of Oxymatrine on Vascular Endothelial Cells from High-Glucose-Induced Cytotoxicity by Inhibiting the Expression of A2B Receptor

2018 ◽  
Vol 45 (2) ◽  
pp. 558-571 ◽  
Author(s):  
Yun Yi ◽  
Yulin Shen ◽  
Qin Wu ◽  
Jingan Rao ◽  
Shu Guan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Viability ◽  
Western Blotting ◽  
High Glucose ◽  
Vascular Endothelial Cells ◽  
Control Group ◽  
Vascular Endothelial ◽  
A2b Receptor ◽  
High Glucose Group ◽  
Glucose Group

Background/Aims: Diabetes mellitus (DM) has become an increasingly epidemic metabolic disease. Vascular endothelial cells play a key role in developing the cardiovascular complications of DM. The A2B receptor is expressed in vascular endothelial cells, and may help regulate the function of endothelial cells. The aim of this study was to investigate the protective effects of oxymatrine (OMT) on human umbilical vein endothelial cells (HUVECs) from high glucose-induced cytotoxicity. Methods: Homology modeling and molecular docking analysis were used to detect the binding sites between the adenosine A2B receptor and OMT. HUVECs were cultured with control (5.5 mM) or elevated glucose (22.2 mM) in the presence or absence of 3 µM OMT or A2B siRNA for 3 days. The MTS cell viability assay was used to measure the toxicity of high glucose on HUVECs and the protective effect of OMT or A2B siRNA. The expression of the adenosine A2B receptor and CCL5 in HUVECs was detected with real-time quantitative PCR (qPCR) and Western blotting methods in each group. Levels of IL-1β and TNF-α were measured using an enzyme-linked immunosorbent assay (ELISA) kit, and the concentration of NO was detected with the nitrate reductase method. Monocyte chemotactic activity in each group was detected using Transwell chambers. Furthermore, the phosphorylation of p38 and ERK1/2 in each group was observed through the Western blotting method. Results: Homology modeling and molecular docking analysis showed that OMT contains well-fitted binding sites to the A2B receptor. After chronic culture at high glucose, the rate of cell viability was significantly lower than that of the control group. After co-treatment with OMT or A2B siRNA, cell viability was significantly increased compared with the high-glucose group. The results from real-time quantitative RT-PCR (qRT-PCR) and Western blotting indicated that high glucose could increase the expression of A2B receptors in HUVECs, an effect that was inhibited by OMT. In addition, the results revealed that the expression of CCL5, IL-1β and TNF-α was increased in the high-glucose group, and that the NO produced by HUVECs decreased due to hyperglycemia; however, co-culture with OMT or A2B siRNA abolished these effects. Meanwhile, the chemotaxis activity of monocytes to HUVECs cultured in high-glucose medium was enhanced 2.59-fold compared to the control cells. However, the inflammatory reactions in HUVECs were completely relieved by co-treatment with OMT or A2B siRNA. Moreover, the phosphorylation of p38 and ERK1/2 in HUVECs in the high-glucose group was significantly higher than that of the control group; these effects were reversed after co-treatment with OMT or A2B siRNA. Conclusion: OMT may protect the HUVECs from high glucose-induced cytotoxicity through inhibitting the expression of A2B receptor and inflammatory factors as well as decreasing the phosphorylation of p38 and ERK1/2.

scholarly journals Involvement of Acid-Sensing Ion Channel 1a Contribute to The Effect of Extracellular Acidosis on Vascular Endothelialcell Damage of Henoch-Schönlein Purpura Patients

2020 ◽  
Author(s):  
Jin-Kun Wang ◽  
Yan Bo ◽  
Qi-lian Zhou ◽  
Li-ping Yuan
Keyword(s):  
Endothelial Cells ◽  
Ion Channel ◽  
Vascular Endothelial Cells ◽  
Binding Activity ◽  
Control Group ◽  
Vascular Endothelial ◽  
Henoch Schonlein Purpura ◽  
Protein Expressions ◽  
Cytoskeleton Protein ◽  
Schonlein Purpura

Abstract Background: Henoch-Schönlein purpura (HSP) is a common kind of systematic vasculitis in children characterized by rash, joint pain,abdominal symptoms and renal disease,the detail pathogenesis of HSP has not been elucidated.Acid-sensing ion channels (ASICs) is a proton-gated sodium selective channel that belongs to Degenerin /epithelial Sodium Channel(DEG/ENaC) superfamily,previous research found the expressions of ASIC1a and ASIC3 in the vascular endothelial cells of HSPThis study aims to investigate the molecular mechanisms of silencing of acid-sensing ion channel 1a(ASIC1a) protects the vascular endothelial cells from Henoch-Schonlein purpura(HSP) patients.Findings:Human dermal microvascular endothelial cells ( HDMVEC) were cultured in vitro, siRNA sequences were designed for the coding region of human ASIC1a gene and HDMVEC cells were transfected with recombinant lentivirus( LV) -sh-ASIC1a. The control group ( NC group) without virus transfection and LV-sh-ASIC1a transfection group ( si-ASIC1a group) were set up. The expression of transfixed ASIC1a gene was detected by RT-PCR. After virus transfection 72 h, serum IgA1from HSP patients and serum IgA1 of normal children were added into HDMVEC cells. ASIC1a and cytoskeleton protein ( sm-α f-actin, MLCK) mRNA and protein expressions were detected by real-time PCR and Western blotting Methods.The binding activity of NF- κB with DNA in HDMVEC was determined by electrophoretic mobility shift assay (EMSA).The whole-cell patch-clamp technique was used to record the current changes and electrophysiological characteristics of ASICs in HDMVEC.Cytoskeleton protein ( sm-α f-actin, MLCK) mRNA and protein expressions in the group of si-ASIC1a group were significantly increased compared with the NC control group( P＜0.01). The HSP serum and silencing of ASIC1a had no significant effect on the binding activity of NF-κB with DNA in HDMVEC. Compared with the NC control group, the ASICS current and calcium overload of the si-ASIC1A group were reduced( P＜0.01) ．Conclusions: Silencing ASIC1a can protect HSP vascular endothelial cell injury by inhibiting ASIC1-related calcium influx and reducing the overload of calcium ,not the NF- κB signaling pathway.

scholarly journals Rat epidermal stem cells promote the angiogenesis of full-thickness wound

2020 ◽  
Author(s):  
Shaobin Huang ◽  
Zhicheng Hu ◽  
Peng Wang ◽  
Yi zhang ◽  
Xiaoling Cao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Endothelial Cells ◽  
Cell Suspension ◽  
Vascular Endothelial Cells ◽  
Control Group ◽  
Vascular Endothelial ◽  
Epidermal Stem Cells ◽  
Full Thickness ◽  
Full Thickness Wound

Abstract Background: Full-thickness wounds are a serious problem which badly affects patients’ life quality and also become the difficult problem for clinicians. Stem cells have great prospects in the treatment of wounds. Our previous experiments proved that autologous basal cell suspension can promote wound healing, and there are epidermal stem cells (ESCs) in basal cell suspension. We then conducted experiments to explore the effect of ESCs on full-thickness wound. Methods: In our study, the rat ESCs were isolated and expanded, and transfected with lentivirus to stably express EGFP. Experimental rats were randomly divided into 2 groups, in the ESCs group, the rat ESCs were sprayed on the Full-thickness wounds of the rats, while in control group, sprayed the PBS on the wound. Wound healing and neovascularization were then evaluated. Colonization, division and differentiation of ESCs on the wound were discovered by immunofluorescence.Results: The result suggested that rat ESCs can colonize, divide and proliferate in the wound. What’s more, the rat ESCs around blood vessels can differentiate into vascular endothelial cells and form a lumen-like structure. Compared with the control group, spraying the rat ESCs on the wound bed can promote angiogenesis and accelerate wound healing. Conclusions: Our study proved that rat ESCs were safe and effective for treating full-thickness wounds, and under certain conditions, ESCs can differentiate into vascular endothelial cells to promote angiogenesis and wound healing.

scholarly journals Effects of IL-1β and TNF-α on the Expression of P311 in Vascular Endothelial Cells and Wound Healing in Mice

2020 ◽  
Vol 11 ◽  
Author(s):  
Daijun Zhou ◽  
Tengfei Liu ◽  
Song Wang ◽  
Weifeng He ◽  
Wei Qian ◽  
...  
Keyword(s):  
Wound Healing ◽  
Endothelial Cells ◽  
Cell Migration ◽  
Protein Expression ◽  
Vascular Endothelial Cells ◽  
Control Group ◽  
Vascular Endothelial ◽  
Expression Levels ◽  
Relative Expression ◽  
Tnf Α

ObjectiveThis study aimed to define the role of interleukine-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the expression of P311 in vascular endothelial cells (VECs) and in wound healing.MethodsDAPI staining, a CCK-8 assay, cell migration assay, and an angiogenesis assay were used to assess the effects exerted by TNF-α and IL-1β at various concentrations on morphology, proliferation, migration, and angiogenesis of VECs. Western blot (WB) and reverse transcription-polymerase chain reaction (RT-PCR) models were employed to observe the effects exerted by proteins related to the nuclear factor-kappa B (NF-κB) signaling pathway and P311 mRNA expression. Bioinformatics analysis was performed on the binding sites of P311 and NF-κB. Finally, to investigate the effects of IL-1β and TNF-α on wound healing and the length of new epithelium in mice, we established a full-thickness wound defect model in mice. Immunohistochemistry was used to measure changes in P311, proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), CD31 (platelet endothelial cell adhesion molecule-1, PECAM-1/CD31), as well as other related proteins.ResultsWhen levels of TNF-α and IL-1β were both 20 ng/ml, their effects on cell proliferation, cytoskeleton protein expression, cell migration, and angiogenesis were the greatest (P &lt; 0.05). IL-1β and TNF-α at moderate concentrations effectively promoted P311 mRNA and p-NF-κB protein expression (P &lt; 0.05), while p-NF-K b protein expression was decreased (P &lt; 0.05). Luciferase assays showed that P311 expression was also relatively greater when stimulated at moderate concentrations (P &lt; 0.05), while relative expression was significantly lower when the p-NF-K b inhibitor CAPE was added (P &lt; 0.05). On 7-day wound healing rate comparison, the control, IL-1β, IL-1βab, TNF-α, and TNF-αab groups were 18, 37, 35, 39, and 36%, respectively, while control group + P311 siRNA was 31% (P &lt; 0.05). New epithelial length, granulation tissue thickness, and number of blood vessels trends were also the same. In the control group, P311 showed lower relative expression levels than the others (P &lt; 0.05). P311 relative expression levels trended as follows: control group &gt; IL-1βab &gt; IL-1β &gt; TNF-αab &gt; TNF-α (P &lt; 0.05).ConclusionWhen IL-1β and TNF-α concentrations are moderate, they effectively promote the proliferation, expression, migration, and angiogenesis of VECs, possibly by promoting the expression of the NF-K b pathway and thereby promoting the expression of P311. In vitro experiments on mice suggest that P311 effectively promotes wound healing, and its mechanism may be closely related to PCNA, CD31, and VEGF.

scholarly journals Early Intervention of Didang Decoction on MLCK Signaling Pathways in Vascular Endothelial Cells of Type 2 Diabetic Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Shoujiao Ye ◽  
Zhenqiang Song ◽  
Jing Li ◽  
Chunshen Li ◽  
Juhong Yang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Protein Kinase ◽  
Early Phase ◽  
Vascular Endothelial Cells ◽  
Late Phase ◽  
Intervention Group ◽  
Control Group ◽  
Vascular Endothelial ◽  
Type 2 Diabetic

In the study, type 2 diabetic rat model was established using streptozotocin (STZ) combined with a high-fat diet, and the rats were divided into control and diabetic groups. Diabetic groups were further divided into nonintervening, simvastatin, Didang Decoction (DDD) early-phase intervening, DDD mid-phase intervening, and DDD late-phase intervening groups. The expression level of MLCK was detected using Western Blot analysis, and the levels of cyclic adenosine monophosphate (cAMP), protein kinase C (PKC), and protein kinase A (PKA) were examined using Real Time PCR. Under the electron microscope, the cells in the early-DDD-intervention group and the simvastatin group were significantly more continuous and compact than those in the diabetic group. Compared with the control group, the expression of cAMP-1 and PKA was decreased in all diabetic groups, whereas the expression of MLCK and PKC was increased in early- and mid-phase DDD-intervening groups (P<0.05); compared with the late-phase DDD-intervening group, the expression of cAMP-1 and PKA was higher, but the level of MLCK and PKC was lower in early-phase DDD-intervening group (P<0.05). In conclusion, the early use of DDD improves the permeability of vascular endothelial cells by regulating the MLCK signaling pathway.

scholarly journals Study on Damage Mechanism and Repair of Vascular Endothelial Cells Based on Ultrasound Technology

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Shuhao Deng ◽  
Quan Jiang ◽  
Xin Lu ◽  
Yuan Zhang
Keyword(s):  
Endothelial Cells ◽  
Endothelial Function ◽  
Relaxation Function ◽  
Vascular Endothelial Cells ◽  
Early Stage ◽  
Gradient Centrifugation ◽  
Control Group ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function

Objective. To detect the endothelial function of external iliac artery in rats with different stages of atherosclerosis by high-resolution ultrasound, so as to provide experimental methodological basis for evaluating the function of vascular endothelial cells by ultrasound. Methods. The animals were randomly divided into the control group ( n = 6 ) and the atherosclerosis model group ( n = 15 ). The atherosclerosis group was further divided into 4-week group, 8-week group, and 12-week group, with 5 animals in each group. After separating and grinding rat spleen, the obtained cells were cultured by density gradient centrifugation. After the cells adhered, the morphology of the cells was observed under a microscope and identified by DiI-Ac-LDL and FITC-UEA-I double staining. The activities of LDH and SOD, the contents of MDA and GSH, and the contents of NO in plasma were detected by biochemical methods. Results. The protective effect of rosanilin on brain injury in rats with acute hypobaric hypoxia and its regulation on the expression of pAkt protein; ox-LDL inhibited the proliferation activity of EPCs in a concentration-dependent manner. The expression of KLF2 and S1PR1 in HAEC can be knocked down by small interfering RNA, and knocking down KLF2 can not only downregulate the expression of S1PR1 but also downregulate HAVEN. With the development of atherosclerosis, the endothelium-dependent relaxation function and endothelium-independent relaxation function of the control group and the atherosclerosis model at 4, 8, and 12 weeks were damaged in different degrees and gradually aggravated. Conclusion. Atherosclerosis is a disease with both morphological and functional damage, and vascular endothelial function is damaged in the early stage with corresponding pathological changes. Ultrasound is an effective method to evaluate vascular endothelial function.

P2X4 receptors mediate ATP-induced calcium influx in human vascular endothelial cells

2000 ◽  
Vol 279 (1) ◽  
pp. H285-H292 ◽  
Author(s):  
Kimiko Yamamoto ◽  
Risa Korenaga ◽  
Akira Kamiya ◽  
Zhi Qi ◽  
Masahiro Sokabe ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Molecular Mechanisms ◽  
Calcium Influx ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Vascular Endothelial ◽  
Protein Levels ◽  
Vasoactive Substances ◽  
Intracellular Ca ◽  
P2x4 Receptors

ATP induces Ca2+ influx across the cell membrane and activates release from intracellular Ca2+ pools in vascular endothelial cells (ECs). Ca2+ signaling leads to the modification of a variety of EC functions, including the production of vasoactive substances such as nitric oxide and prostacyclin. However, the molecular mechanisms for ATP-induced Ca2+ influx in ECs have not been thoroughly clarified. Here we demonstrate evidence that a P2X4receptor for an ATP-gated cation channel is predominantly expressed in human ECs and is involved in the ATP-induced Ca2+ influx. Northern blot analysis distinctly showed the expression of P2X4 mRNA in human ECs cultured from the umbilical vein, aorta, pulmonary artery, and skin microvessels. Competitive PCR revealed that P2X4 mRNA expression was much higher in ECs than was the expression of other subtypes, including P2X1, P2X3, P2X5, and P2X7. Treatment of ECs with antisense oligonucleotides designed to target the P2X4 receptor decreased the P2X4 mRNA and protein levels to ∼25% of control levels and markedly prevented the ATP-induced Ca2+ influx.

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