scholarly journals Extracellular HtrA2 Induces Apoptosis in Human Umbilical Vein Endothelial Cells

2019 ◽  
Vol 20 (21) ◽  
pp. 5446
Author(s):  
Kaur ◽  
Stallmann ◽  
Schanze ◽  
Laumann ◽  
Heger ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Ischemia Reperfusion ◽  
Annexin V ◽  
Myocardial Damage ◽  
Human Umbilical Vein ◽  
St Segment Elevation ◽  
Induced Apoptosis ◽  
Umbilical Vein Endothelial Cells

The serine protease high-temperature-required protein A2 (HtrA2) has been identified as a key intracellular molecule promoting apoptosis in cells during ischemia reperfusion (IR) injury. IR injury in ST-segment elevation myocardial infarction (STEMI) contributes to overall myocardial damage. HtrA2 has further been shown to be significantly increased in the serum of patients with STEMI. In the present pilot study, we use human umbilical vein endothelial cells (HUVECs) to investigate whether extracellular HtrA2 induces apoptosis using Annexin V staining. Furthermore, we examine whether HtrA2 is released extracellularly after staurosporine-induced apoptosis using ELISA. We find that HtrA2 is released upon induction of apoptosis by staurosporine into the cell culture medium. Furthermore, treatment of HUVECs with extracellular HtrA2-induces apoptosis, while the addition of anti-HtrA2 antibodies reduces both HtrA2- and staurosporine-induced endothelial cell apoptosis. In conclusion, we show here that extracellular HtrA2 induces apoptosis in human endothelial cells, although the exact molecular mechanisms have to be investigated in future.

scholarly journals Berberine Protects Human Umbilical Vein Endothelial Cells against LPS-Induced Apoptosis by Blocking JNK-Mediated Signaling

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Junping Guo ◽  
Lijun Wang ◽  
Linyao Wang ◽  
Senmi Qian ◽  
Dayong Zhang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Specific Inhibitor ◽  
Cell Counting ◽  
Potential Candidate ◽  
Sod Activity ◽  
Human Umbilical Vein ◽  
Induced Apoptosis ◽  
Umbilical Vein Endothelial Cells

Endothelial dysfunction is a critical factor during the initiation of atherosclerosis. Berberine has a beneficial effect on endothelial function; however, the underlying mechanisms remain unclear. In this study, we investigated the effects of berberine on lipopolysaccharide- (LPS-) induced apoptosis in human umbilical vein endothelial cells (HUVECs) and the molecular mechanisms mediating the effect. The effects of berberine on LPS-induced cell apoptosis and viability were measured with 5-ethynyl-2′-deoxyuridine staining, flow cytometry, and Cell Counting Kit-8 assays. The expression and/or activation of proapoptotic and antiapoptotic proteins or signaling pathways, including caspase-3, poly(ADP-ribose) polymerase, myeloid cell leukemia-1 (MCL-1), p38 mitogen-activated protein kinase, C-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase, were determined with western blotting. The malondialdehyde levels, superoxide dismutase (SOD) activity, and production of proinflammatory cytokines were measured with enzyme-linked immunosorbent assays. The results demonstrated that berberine pretreatment protected HUVECs from LPS-induced apoptosis, attenuated LPS-induced injury, inhibited LPS-induced JNK phosphorylation, increased MCL-1 expression and SOD activity, and decreased proinflammatory cytokine production. The effects of berberine on LPS-treated HUVECs were prevented by SP600125, a JNK-specific inhibitor. Thus, berberine might be a potential candidate in the treatment of endothelial cell injury-related vascular diseases.

scholarly journals Hypoxic human umbilical vein endothelial cells induce activation of adherent polymorphonuclear leukocytes

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3705-3716 ◽  
Author(s):  
T Arnould ◽  
C Michiels ◽  
J Remacle
Keyword(s):  
Endothelial Cells ◽  
Superoxide Dismutase ◽  
Superoxide Anion ◽  
Calcium Concentration ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Superoxide Anion Production ◽  
Elastase Inhibitor ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

Abstract Several pieces of evidence are reported for the accumulation of activated neutrophils in ischemic and reperfused tissues leading to the transformation of the ischemic tissue into an inflammatory territory and to an enhancement of tissue damages during reoxygenation. However, the molecular mechanisms responsible for these observations and the precise role played by endothelial cells in this process are still poorly understood. In this study, an in vitro model that mimics this situation was used to investigate the effects of hypoxia-incubated human umbilical vein endothelial cells (HUVEC) on polymorphonuclear leukocyte (PMN) functions. A strong PMN activation characterized by an increase in intracellular calcium concentration as well as by superoxide anion release and leukotriene B4 production was observed when these cells were coincubated with hypoxic HUVEC. On the other hand, conditioned medium from hypoxia-incubated HUVEC failed to activate PMN, as determined by the lack of PMN calcium concentration increase, the failure of superoxide anion production enhancement, as well as the absence of effects on the integrin CD18, CD11a, and CD11b expression. These results indicate that the presence of hypoxia- incubated HUVEC is necessary to obtain an activation of the PMN, probably via the adherence process. Once activated by coincubation with hypoxic HUVEC, PMN became cytotoxic, as evidenced by 51Cr released from prelabeled HUVEC. This cytotoxic effect of activated PMN for hypoxic endothelial cells could be prevented by a combination of superoxide dismutase and catalase (94% inhibition), whereas superoxide dismutase alone was inefficient. Antiprotease (alpha 2-macroglobulin) and a specific elastase inhibitor (MAAPV-CMK) were also inefficient. These results correlate very well with the fact that no increase in elastase release could be observed in supernatants from PMN coincubated with hypoxic HUVEC. Furthermore, when adherence process was blocked by oleic acid or by anti-ICAM-1 monoclonal antibodies, protection was, respectively, 90% and 72%. We thus evidenced that free radicals but not elastase released from activated PMN coincubated with hypoxic HUVEC are involved in HUVEC injury. We conclude from these results that PMN activation is initiated by PMN adherence to hypoxic HUVEC. These observations indicate that hypoxic HUVEC may be partly responsible for neutrophil activation observed in ischemic tissues, which is part of the amplification process of tissue damage.

scholarly journals Secoisolariciresinol Diglucoside Exerts Anti-Inflammatory and Antiapoptotic Effects through Inhibiting the Akt/IκB/NF-κB Pathway on Human Umbilical Vein Endothelial Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Shaoyang Zhang ◽  
Meili Cheng ◽  
Zhen Wang ◽  
Yuzhi Liu ◽  
Yuhua Ren ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Ischemia Reperfusion ◽  
Tube Formation ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay ◽  
Secoisolariciresinol Diglucoside ◽  
Human Umbilical Vein ◽  
No Release ◽  
Umbilical Vein Endothelial Cells

Inflammation is a key regulator in the progression of atherosclerosis (AS) which extremely affects people’s health. Secoisolariciresinol diglucoside (SDG), a plant lignan, is relevant to angiogenesis and cardioprotection against ischemia-reperfusion injury and improves vascular disorders. However, the effect of SDG on cardiovascular disorder is not clear. In the present study, we aimed to investigate the effects of SDG on lipopolysaccharide- (LPS-) stimulated Human Umbilical Vein Endothelial Cells (HUVECs) and elucidate the underlying mechanism. The LPS-stimulated HUVEC cellular model was established. The cell viability, the cell tube formation activity, the nitric oxide (NO) release, the levels of inflammatory cytokine interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), the activation of nuclear factor kappa-B (NF-κB) pathway, and the expression of protein kinase B (Akt) were determined using Cell Counting Kit-8, cell tube-formation assay, western blotting, and enzyme-linked immunosorbent assay. Our results revealed that SDG reduces the angiogenic capacity of HUVECs and inhibited LPS-mediated HUVEC injury and apoptosis. In addition, SDG increased NO release and decreased the levels of IL-1β, IL-6, and TNF-α in LPS-treated HUVECs. Meanwhile, SDG inhibited the NF-κB pathway and downregulated Akt expression in LPS-induced HUVECs. Our results indicated that SDG relieves LPS-mediated HUVEC injury by inhibiting the NF-κB pathway which is partly dependent on the disruption of Akt activation. Therefore, SDG exerts its cytoprotective effects in the context of LPS-treated HUVECs via regulation of the Akt/IκB/NF-κB pathway and may be a potential treatment drug for cardiovascular disease.

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