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 Novel Anti-inflammatory Effects of Canagliflozin Involving Hexokinase II in Lipopolysaccharide-Stimulated Human Coronary Artery Endothelial Cells

2020 ◽  
Author(s):  
Laween Uthman ◽  
Marius Kuschma ◽  
Gregor Römer ◽  
Marleen Boomsma ◽  
Jens Kessler ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Coronary Artery ◽  
Inflammatory Responses ◽  
Vascular Inflammation ◽  
Glycolytic Enzyme ◽  
Human Coronary Artery ◽  
Hexokinase Ii ◽  
Protein Levels ◽  
Inflammatory Mechanism ◽  
Anti Inflammatory

Abstract Purpose Vascular inflammation and disturbed metabolism are observed in heart failure and type 2 diabetes mellitus. Glycolytic enzyme hexokinase II (HKII) is upregulated by inflammation. We hypothesized that SGLT2 inhibitors Canagliflozin (Cana), Empagliflozin (Empa) or Dapagliflozin (Dapa) reduces inflammation via HKII in endothelial cells, and that HKII-dependent inflammation is determined by ERK1/2, NF-κB. and/or AMPK activity in lipopolysaccharide (LPS)-stimulated human coronary artery endothelial cells (HCAECs). Methods HCAECs were pre-incubated with 3 μM or 10 μM Cana, 1 μM, 3 μM or 10 μM Empa or 0.5 μM, 3 μM or 10 μM Dapa (16 h) and subjected to 3 h LPS (1 μg/mL). HKII was silenced via siRNA transfection. Interleukin-6 (IL-6) release was measured by ELISA. Protein levels of HK I and II, ERK1/2, AMPK and NF-κB were detected using infra-red western blot. Results LPS increased IL-6 release and ERK1/2 phosphorylation; Cana prevented these pro-inflammatory responses (IL-6: pg/ml, control 46 ± 2, LPS 280 ± 154 p < 0.01 vs. control, LPS + Cana 96 ± 40, p < 0.05 vs. LPS). Cana reduced HKII expression (HKII/GAPDH, control 0.91 ± 0.16, Cana 0.71 ± 0.13 p < 0.05 vs. control, LPS 1.02 ± 0.25, LPS + Cana 0.82 ± 0.24 p < 0.05 vs. LPS). Empa and Dapa were without effect on IL-6 release and HKII expression in the model used. Knockdown of HKII by 37% resulted caused partial loss of Cana-mediated IL-6 reduction (pg/ml, control 35 ± 5, LPS 188 ± 115 p < 0.05 vs. control, LPS + Cana 124 ± 75) and ERK1/2 activation by LPS. In LPS-stimulated HCAECs, Cana, but not Empa or Dapa, activated AMPK. AMPK activator A769662 reduced IL-6 release. Conclusion Cana conveys anti-inflammatory actions in LPS-treated HCAECs through 1) reductions in HKII and ERK1/2 phosphorylation and 2) AMPK activation. These data suggest a novel anti-inflammatory mechanism of Cana through HKII.

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

Role of hyperlipidemia in atherosclerotic plaque formation in the internal carotid artery

2006 ◽  
Vol 34 (6) ◽  
pp. 283-288 ◽  
Author(s):  
Levente Kerenyi ◽  
Laszlo Mihalka ◽  
Laszlo Csiba ◽  
Hajnalka Bacso ◽  
Daniel Bereczki
Keyword(s):  
Carotid Artery ◽  
Internal Carotid Artery ◽  
Atherosclerotic Plaque ◽  
Internal Carotid ◽  
Plaque Formation ◽  
Atherosclerotic Plaque Formation

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.

scholarly journals Endothelial Nitric Oxide Synthase (eNOS) S1176 phosphorylation status governs atherosclerotic lesion formation

2022 ◽  
Author(s):  
Monica Y Lee ◽  
Nur-Taz Rahman ◽  
Bill Sessa
Keyword(s):  
Atherosclerotic Plaque ◽  
Phosphorylation Site ◽  
Plaque Formation ◽  
Mutant Mice ◽  
Single Amino Acid ◽  
No Production ◽  
Loss Of Function ◽  
Gain Of Function ◽  
Atherosclerotic Plaque Formation

Objective: We have previously demonstrated the in vivo importance of the Akt-eNOS substratekinase relationship, as defective postnatal angiogenesis characteristic of global Akt1-null mice is rescued when bred to gain-of-function eNOS S1176D mutant mice. While multiple studies support the cardioprotective role of endothelial NO generation, the causal role of Akt1-dependent eNOS S1176 phosphorylation during atherosclerotic plaque formation is not yet clear. Approach & Results: We herein bred congenic loss-of-function eNOS S1176A and gain-of function eNOS S1176D mutant mice to the proatherogenic Akt1-/-; ApoE-/- double knockout mice to definitively test the importance of Akt-mediated eNOS S1176 phosphorylation during atherogenesis. We find that a single amino acid substitution at the eNOS S1176 phosphorylation site yields divergent effects on atherosclerotic plaque formation, as an eNOS phospho-mimic aspartate (D) substitution at S1176 leads to decreased indices of atherosclerosis, even when on a proatherogenic Akt1 global deletion background. Conversely, mice harboring an unphosphorylatable mutation to alanine (S1176A) result in increased lipid deposition and cellular apoptosis, phenocopying the physiological consequence of eNOS deletion and/or impaired enzyme function. Furthermore, gene expression analyses of whole aortas indicate a combinatorial detriment from NO deficiency and Western Diet challenge, as loss-of-function eNOS SA mice on a high-fat and high-cholesterol diet present a unique expression pattern indicative of augmented T-cell activity when compared to eNOS S1176D mice. Conclusions: By using genetic epistasis approaches, we conclusively demonstrate that Akt mediated eNOS S1176 phosphorylation and subsequent activation remains to be the most physiologically relevant method of NO production to promote cardioprotective effects.

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