Proapoptotic effects of ANG II in human coronary artery endothelial cells: role of AT1receptor and PKC activation

1999 ◽  
Vol 276 (3) ◽  
pp. H786-H792 ◽  
Author(s):  
Dayuan Li ◽  
Baichun Yang ◽  
M. Ian Philips ◽  
Jawahar L. Mehta
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
Specific Inhibitor ◽  
Ang Ii ◽  
Human Coronary Artery ◽  
Tnf Α ◽  
Factor Α ◽  
Pkc Activation

Anoxia-reoxygenation, tumor necrosis factor-α (TNF-α), and angiotensin II (ANG II) have been shown to induce apoptosis in myocytes. However, the role of these mediators in causing apoptosis of human coronary artery endothelial cells (HCAEC) is not known. This study was designed to examine the interaction of these mediators in induction of apoptosis in HCAEC. Cultured HCAEC were exposed to anoxia-reoxygenation, TNF-α, and ANG II. TNF-α enhanced apoptosis of HCAEC (determined by DNA nick-end labeling in situ and DNA laddering) caused by anoxia-reoxygenation. ANG II increased apoptosis beyond that caused by anoxia-reoxygenation and TNF-α. Apoptosis caused by ANG II was reduced by losartan, a specific ANG II type 1 receptor (AT1R) blocker, whereas PD-123,177, a specific ANG II type 2 receptor blocker, under identical conditions had minimal effect. The proapoptotic effects of ANG II were associated with the activation of protein kinase C (PKC). The importance of PKC activation as a signal transduction mechanism became evident in experiments wherein treatment of HCAEC with a specific inhibitor of PKC activation decreased ANG II-mediated apoptosis. Thus AT1R activation appears to be responsible for apoptosis caused by ANG II in HCAEC, and AT1R activation-mediated apoptosis involves activation of PKC.

Inhibition of Pro-Inflammatory Cytokine Secretion by Select Antioxidants in Human Coronary Artery Endothelial Cells

2020 ◽  
Vol 90 (1-2) ◽  
pp. 103-112 ◽  
Author(s):  
Michael J. Haas ◽  
Marilu Jurado-Flores ◽  
Ramadan Hammoud ◽  
Victoria Feng ◽  
Krista Gonzales ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Ascorbic Acid ◽  
Coronary Artery ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Culture Media ◽  
Cytokine Secretion ◽  
Human Coronary Artery ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

Abstract. Inflammatory and oxidative stress in endothelial cells are implicated in the pathogenesis of premature atherosclerosis in diabetes. To determine whether high-dextrose concentrations induce the expression of pro-inflammatory cytokines, human coronary artery endothelial cells (HCAEC) were exposed to either 5.5 or 27.5 mM dextrose for 24-hours and interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor α (TNF α) levels were measured by enzyme immunoassays. To determine the effect of antioxidants on inflammatory cytokine secretion, cells were also treated with α-tocopherol, ascorbic acid, and the glutathione peroxidase mimetic ebselen. Only the concentration of IL-1β in culture media from cells exposed to 27.5 mM dextrose increased relative to cells maintained in 5.5 mM dextrose. Treatment with α-tocopherol (10, 100, and 1,000 μM) and ascorbic acid (15, 150, and 1,500 μM) at the same time that the dextrose was added reduced IL-1β, IL-6, and IL-8 levels in culture media from cells maintained at 5.5 mM dextrose but had no effect on IL-1β, IL-6, and IL-8 levels in cells exposed to 27.5 mM dextrose. However, ebselen treatment reduced IL-1β, IL-6, and IL-8 levels in cells maintained in either 5.5 or 27.5 mM dextrose. IL-2 and TNF α concentrations in culture media were below the limit of detection under all experimental conditions studied suggesting that these cells may not synthesize detectable quantities of these cytokines. These results suggest that dextrose at certain concentrations may increase IL-1β levels and that antioxidants have differential effects on suppressing the secretion of pro-inflammatory cytokines in HCAEC.

scholarly journals TNF-α-Induced YAP/TAZ Activity Mediates Leukocyte-Endothelial Adhesion by Regulating VCAM1 Expression in Endothelial Cells

2018 ◽  
Vol 19 (11) ◽  
pp. 3428 ◽  
Author(s):  
Hyun-Jung Choi ◽  
Na-Eun Kim ◽  
Byeong Kim ◽  
Miran Seo ◽  
Ji Heo
Keyword(s):  
Endothelial Cells ◽  
Rho Gtpases ◽  
Leukocyte Adhesion ◽  
Hippo Pathway ◽  
Specific Inhibitor ◽  
Vascular Diseases ◽  
Adhesive Properties ◽  
Sprouting Angiogenesis ◽  
Tnf Α

YAP/TAZ, a transcriptional co-activator of Hippo pathway, has emerged as a central player in vessel homeostasis such as sprouting angiogenesis and vascular barrier stabilization, during development. However, the role of YAP/TAZ in pathological angiogenesis remains unclear. Here, we demonstrated that YAP/TAZ is a critical mediator in leukocyte-endothelial adhesion induced by the vascular inflammatory cytokine TNF-α. YAP/TAZ was dephosphorylated, translocated from the cytosol to the nucleus, and activated by TNF-α in endothelial cells. A specific inhibitor of Rho GTPases suppressed the TNF-α-induced dephosphorylation of YAP. Knockdown of YAP/TAZ using siRNA significantly reduced the expression of the leukocyte adhesion molecule VCAM1 induced by TNF-α. The adhesion of monocytes to endothelial cells was also markedly reduced by YAP/TAZ silencing. However, knockdown of YAP/TAZ did not affect TNF-α-induced NF-κB signaling. Overall, these results suggest that YAP/TAZ plays critical roles in regulating TNF-α-induced endothelial cell adhesive properties without affecting the NF-κB pathway, and implicate YAP/TAZ as a potential therapeutic target for treating inflammatory vascular diseases.

scholarly journals Interleukin-37: The Effect of Anti-Inflammatory Response in Human Coronary Artery Endothelial Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Xianfeng Yan ◽  
Bin Xie ◽  
Guihai Wu ◽  
Jing Hu ◽  
Di Wang ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Endothelial Cells ◽  
Coronary Artery ◽  
Inflammatory Response ◽  
Atherosclerotic Plaque ◽  
Inflammatory Responses ◽  
Plaque Formation ◽  
Human Coronary Artery ◽  
Atherosclerotic Plaque Formation

Interleukin-37 (IL-37) is unique in the IL-1 family since it broadly suppresses innate immunity and elevates in humans with inflammatory and autoimmune diseases. IL-37 shows definite groups and transcripts for human IL37 gene, but it is still not completely understood the effect and mechanisms of inflammatory response in endothelial cells. It is well accepted that endothelial dysfunction caused by inflammation is a key initiating event in atherosclerotic plaque formation, which leads to the occurrence and development of the cardiovascular adverse events in clinical since the inflammatory responses of endothelial cells could induce and enhance the deposition of extensive lipid and the formation of atherosclerotic plaque in the intima. Thus, it is essential to investigate the role and potential mechanisms in endothelial inflammatory response to prevent the formation and development of many cardiovascular diseases including atherosclerosis. So far, the recent studies have revealed that IL-37 is able to inhibit inflammatory response by suppressing the TLR2-NF-κB-ICAM-1 pathway intracellularly in human coronary artery endothelial cells (HCAECs). Further, the role of IL-37 may be related to the IL-18 pathway extracellularly and involved in the adhesion and transmigration of neutrophils in HCAECs.

scholarly journals Role of Caspases in Ox-LDL–Induced Apoptotic Cascade in Human Coronary Artery Endothelial Cells

2004 ◽  
Vol 94 (3) ◽  
pp. 370-376 ◽  
Author(s):  
Jiawei Chen ◽  
Jawahar L. Mehta ◽  
Nezam Haider ◽  
Xingjian Zhang ◽  
Jagat Narula ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
Human Coronary Artery ◽  
Apoptotic Cascade

scholarly journals Activation of angiotensin II type 2 receptor suppresses TNF-α-induced ICAM-1 via NF-кB: possible role of ACE2

2015 ◽  
Vol 309 (5) ◽  
pp. H827-H834 ◽  
Author(s):  
Liping Zhu ◽  
Oscar A. Carretero ◽  
Jiang Xu ◽  
Pamela Harding ◽  
Nithya Ramadurai ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Ang Ii ◽  
Human Coronary Artery ◽  
Activity Inhibition ◽  
Tnf Α ◽  
System Activation ◽  
Interfering Rna ◽  
Stimulation Of

ANG II type 2 receptor (AT2) and ANG I-converting enzyme 2 (ACE2) are important components of the renin-ANG system. Activation of AT2 and ACE2 reportedly counteracts proinflammatory effects of ANG II. However, the possible interaction between AT2 and ACE2 has never been established. We hypothesized that activation of AT2 increases ACE2 activity, thereby preventing TNF-α-stimulated ICAM-1 expression via inhibition of NF-κB signaling. Human coronary artery endothelial cells were pretreated with AT2 antagonist PD123319 (PD) or ACE2 inhibitor DX600 and then stimulated with TNF-α in the presence or absence of AT2 agonist CGP42112 (CGP). We found that AT2 agonist CGP increased both ACE2 protein expression and activity. This effect was blunted by AT2 antagonist PD. ICAM-1 expression was very low in untreated cells but greatly increased by TNF-α. Activation of AT2 with agonist CGP or with ANG II under concomitant AT1 antagonist reduced TNF-α-induced ICAM-1 expression, which was reversed by AT2 antagonist PD or ACE2 inhibitor DX600 or knockdown of ACE2 with small interfering RNA. AT2 activation also suppressed TNF-α-stimulated phosphorylation of inhibitory κB (p-IκB) and NF-κB activity. Inhibition of ACE2 reversed the inhibitory effect of AT2 on TNF-α-stimulated p-IκB and NF-κB activity. Our findings suggest that stimulation of AT2 reduces TNF-α-stimulated ICAM-1 expression, which is partly through ACE2-mediated inhibition of NF-κB signaling.

Abstract 190: Purinergic Control of Tissue Factor Transcription in Human Coronary Artery Endothelial Cells: New AP-1 Site and Negative Regulator

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Yiwei Liu ◽  
Lingxin Zhang ◽  
Chuan Wang ◽  
Shama Roy ◽  
Jianzhong Shen
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
Tissue Factor ◽  
Promoter Activity ◽  
Purinergic Receptor ◽  
Consensus Sequence ◽  
Negative Regulator ◽  
Coagulation Cascade ◽  
Human Coronary Artery

Previously we reported that the P2Y2 receptor (P2Y2R) is one of the predominant purinergic receptors expressed in human coronary artery endothelial cells (HCAEC), and that P2Y2R activation by ATP or UTP induces dramatic up-regulation of tissue factor (TF), key initiator of the coagulation cascade. However, the molecular mechanism of this P2Y2R-TF axis remains unclear. Here we report a role of a newly identified AP-1 consensus sequence along with its new binding components in P2Y2R regulation of TF transcription. We identified with bioinformatics tools that a novel AP-1 site at -1363 bp of human TF promoter region is highly conserved across multiple species. P2Y2R activation increased TF promoter activity and mRNA expression in HCAEC. Truncation, deletion, and mutation of this new distal AP-1 site all significantly supressed TF promoter activity in response to P2Y2R activation. EMSA and ChIP assays further confirmed that upon P2Y2R activation, c-Jun, ATF-2 and Fra-1, but not the typical c-Fos, bound to the new AP-1 site. In addition, loss-of-function studies using siRNAs confirmed a positive transactivation role of c-Jun and ATF-2, but unexpectedly revealed a strong negative role of Fra-1 in P2Y2R-induced TF up-regulation. Furthermore, we found that P2Y2R activation promoted ERK1/2 phosphorylation, leading to Fra-1 activation while JNK activated c-Jun and ATF-2. These findings reveal the basis for P2Y purinergic receptor regulation of endothelial TF expression and indicate that targeting the P2Y2R-Fra-1-TF pathway may be an attractive new strategy in control of vascular thrombogenicity and/or inflammation associated with endothelial dysfunction.

High-Dose IgG Completely Inhibited TNF-α-Induced, but Not IL-1β- or Poly (I:C)-Induced, G-CSF Expression by Human Coronary Artery Endothelial Cells

2013 ◽  
Vol 131 (2) ◽  
pp. AB38
Author(s):  
Akio Matsuda ◽  
Hideaki Morita ◽  
Hirotoshi Unno ◽  
Hirohisa Saito ◽  
Kenji Matsumoto ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
Poly I:C ◽  
High Dose ◽  
Human Coronary Artery ◽  
Tnf Α
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