Abstract 61: Anti-inflammatory Effect Of Resveratrol In Human Coronary Arterial Endothelial Cells Via Autophagy: Implication For The Treatment Of Kawasaki Disease

Circulation ◽  
2015 ◽  
Vol 131 (suppl_2) ◽  
Author(s):  
Fu-Chen Huang Huang ◽  
Ho-Chang Kuo ◽  
Hong-Ren Yu
Keyword(s):  
Endothelial Cells ◽  
Kawasaki Disease ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cellular Adhesion ◽  
Tnf Alpha ◽  
Coronary Aneurysms ◽  
Cellular Adhesion Molecule ◽  
Increased Risk ◽  
Anti Inflammatory

Kawasaki disease (KD) is an acute febrile vasculitis of childhood and is the leading cause of acquired heart disease in children in the developed world. If untreated, KD can result in coronary aneurysms in 25% of patients, who are at risk of myocardial infarction, sudden death, and congestive heart failure. Despite the success, 10-20% of children will have persistent or recrudescent fever after their first infusion of IVIG. These patients are at increased risk of developing coronary artery abnormalities. Additional therapies should be explored to decrease the incidence of coronary arteritis complication and improve the prognosis in Kawasaki disease. Induced autophagy with resveratrol confers cardioprotection during ischemia and reperfusion in rats. KD is associated with elevated production of inflammatory cytokines, causing damage to the coronary arteries. Serum TNF-alpha levels are elevated in KD, which was supposed to activate the endothelial cells. As a result, adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular cellular adhesion molecule-1(VCAM-1) are expressed in the endothelial cells, and leucocytes adhere firmly to endothelial cells. The leucocytes then damage the endothelial cells and smooth muscle cells and cause vasculitis. In this study, we examined the anti-inflammatory effects of resveratrol on TNF-alpha-induced adhesion molecule expression (VCAM-1 and ICAM-1) and cytokine production (interleukin (IL)-1beta, IL-6 and IL-8) in HCAECs. Pretreatment with resveratrol significantly inhibited TNF-alpha-induced adhesion molecules and cytokines production in HCAECs via the activation of autophagy. Our results suggest that adjunctive resveratrol therapy may modulate the inflammatory response during KD vasculitis and explore the role of autophagy in the pathogenesis of the complication and the promising therapy.

Adenosine inhibits cytokine release and expression of adhesion molecules by activated human endothelial cells

1996 ◽  
Vol 270 (2) ◽  
pp. C522-C529 ◽  
Author(s):  
M. G. Bouma ◽  
F. A. van den Wildenberg ◽  
W. A. Buurman
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Vascular Endothelium ◽  
Cell Activation ◽  
Umbilical Vein ◽  
Intercellular Adhesion Molecule ◽  
Cytokine Release ◽  
Adenosine Deaminase Activity ◽  
Anti Inflammatory

Ischemia induces excessive ATP catabolism with subsequent local release of its metabolite adenosine, an autacoid with anti-inflammatory properties. Because activation of the vascular endothelium is critical to the inflammatory host response during ischemia and reperfusion, the effects of adenosine on two major determinants of endothelial cell activation (i.e., the release of proinflammatory cytokines and the expression of adhesion molecules) were studied. Adenosine dose dependently inhibited the release of interleukin (IL)-6 and IL-8 by stimulated human umbilical vein endothelial cells (HUVEC). Expression of E-selectin and vascular cell adhesion molecule 1 (VCAM-1), but not intercellular adhesion molecule 1 (ICAM-1), by activated HUVEC was also reduced by adenosine. Inhibition of endogenous adenosine deaminase activity by erythro-9-(2-hydroxy-3-nonyl)adenine or 2'-deoxycoformycin strongly enhanced the inhibitory effects of exogenous adenosine on cytokine release and expression of E-selectin and VCAM-1. However, a clear role for specific adenosine receptors in the described inhibitory events could not be established. Together, these data imply that the vascular endothelium constitutes an important target for the anti-inflammatory actions of adenosine.

Importance of adhesion molecules for children with congenital heart disease

2012 ◽  
Vol 23 (1) ◽  
pp. 35-40
Author(s):  
Ayşe Yıldırım ◽  
Aysu T. Karaağaç ◽  
Fusun Güzelmeriç ◽  
Nihat Çine ◽  
Naci C. Öner
Keyword(s):  
Blood Flow ◽  
Pulmonary Hypertension ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Pulmonary Blood Flow ◽  
Congenital Heart ◽  
Heart Diseases ◽  
Cellular Adhesion ◽  
Mean Values ◽  
Cellular Adhesion Molecule

AbstractBackgroundThe aim of our study was to compare the blood levels of adhesion molecules in children with different heart diseases and pulmonary flow rates.MethodsIn this study, we evaluated the levels of soluble intercellular adhesion molecule-1 and soluble vascular cellular adhesion molecule-1 in blood samples of 65 children with different congenital heart diseases. The patients were divided into four groups according to their pulmonary blood flow. The first group had increased pulmonary blood flow with pulmonary hypertension and left-to-right shunt. The second group had increased pulmonary blood flow without pulmonary hypertension and left-to-right shunt. The third group had decreased pulmonary blood flow with cyanotic congenital heart disease and the fourth group had normal pulmonary blood flow with left ventricle outflow tract obstruction and aortic stenosis.ResultThe highest soluble intercellular and vascular cellular adhesion molecule-1 levels with the mean values of 420.2 nanograms per millilitre and 1382.1 nanograms per millilitre, respectively, were measured in the first group and the lowest levels with the mean values of 104.4 and 358.6 nanograms per millilitre, respectively, were measured in the fourth group. The highest pulmonary blood pressure levels were found in the first group.ConclusionEndothelial activity is influenced not only by left-to-right shunt with pulmonary hypertension, but also by decreased pulmonary blood flow in cyanotic heart diseases. Adhesion molecules are valuable markers of endothelial activity in congenital heart diseases, and they are influenced by pulmonary blood flow rate.

scholarly journals The Hinge-Helix 1 Region of Peroxisome Proliferator-Activated Receptor γ1 (PPARγ1) Mediates Interaction with Extracellular Signal-Regulated Kinase 5 and PPARγ1 Transcriptional Activation: Involvement in Flow-Induced PPARγ Activation in Endothelial Cells

2004 ◽  
Vol 24 (19) ◽  
pp. 8691-8704 ◽  
Author(s):  
Masashi Akaike ◽  
Wenyi Che ◽  
Nicole-Lerner Marmarosh ◽  
Shinsuke Ohta ◽  
Masaki Osawa ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Critical Role ◽  
Physiological Role ◽  
Cellular Adhesion ◽  
Dominant Negative ◽  
Peroxisome Proliferator ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Cellular Adhesion Molecule

ABSTRACT Peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors that form a subfamily of the nuclear receptor gene family. Since both flow and PPARγ have atheroprotective effects and extracellular signal-regulated kinase 5 (ERK5) kinase activity is significantly increased by flow, we investigated whether ERK5 kinase regulates PPARγ activity. We found that activation of ERK5 induced PPARγ1 activation in endothelial cells (ECs). However, we could not detect PPARγ phosphorylation by incubation with activated ERK5 in vitro, in contrast to ERK1/2 and JNK, suggesting a role for ERK5 as a scaffold. Endogenous PPARγ1 was coimmunoprecipitated with endogenous ERK5 in ECs. By mammalian two-hybrid analysis, we found that PPARγ1 associated with ERK5a at the hinge-helix 1 region of PPARγ1. Expressing a hinge-helix 1 region PPARγ1 fragment disrupted the ERK5a-PPARγ1 interaction, suggesting a critical role for hinge-helix 1 region of PPARγ in the ERK5-PPARγ interaction. Flow increased ERK5 and PPARγ1 activation, and the hinge-helix 1 region of the PPARγ1 fragment and dominant negative MEK5β significantly reduced flow-induced PPARγ activation. The dominant negative MEK5β also prevented flow-mediated inhibition of tumor necrosis factor alpha-mediated NF-κB activation and adhesion molecule expression, including vascular cellular adhesion molecule 1 and E-selectin, indicating a physiological role for ERK5 and PPARγ activation in flow-mediated antiinflammatory effects. We also found that ERK5 kinase activation was required, likely by inducing a conformational change in the NH2-terminal region of ERK5 that prevented association of ERK5 and PPARγ1. Furthermore, association of ERK5a and PPARγ1 disrupted the interaction of SMRT and PPARγ1, thereby inducing PPARγ activation. These data suggest that ERK5 mediates flow- and ligand-induced PPARγ activation via the interaction of ERK5 with the hinge-helix 1 region of PPARγ.

scholarly journals Interactions of TLR4 and PPARγ, Dependent on AMPK Signalling Pathway Contribute to Anti-Inflammatory Effects of Vaccariae Hypaphorine in Endothelial Cells

2017 ◽  
Vol 42 (3) ◽  
pp. 1227-1239 ◽  
Author(s):  
Haijian Sun ◽  
Xuexue Zhu ◽  
Wei Lin ◽  
Yuetao Zhou ◽  
Weiwei Cai ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Inflammatory Cytokines ◽  
Cellular Adhesion ◽  
Signalling Pathway ◽  
Peroxisome Proliferator ◽  
Atherosclerotic Cardiovascular Disease ◽  
Pparγ Agonist ◽  
Cellular Adhesion Molecule ◽  
Tnf Α ◽  
Anti Inflammatory

Background /Aims: Accumulating evidence indicates that endothelial inflammation is one of the critical determinants in pathogenesis of atherosclerotic cardiovascular disease. Our previous studies had demonstrated that Vaccariae prevented high glucose or oxidative stress-triggered endothelial dysfunction in vitro. Very little is known about the potential effects of hypaphorine from Vaccariae seed on inflammatory response in endothelial cells. Methods: In the present study, we evaluated the anti-inflammatory effects of Vaccariae hypaphorine (VH) on lipopolysaccharide (LPS)-challenged endothelial EA.hy926 cells. The inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), monocyte chemoattractant protein 1 (MCP-1) and vascular cellular adhesion molecule-1 (VCAM-1) were measured by real-time PCR (RT-PCR). The expressions of adenosine monophosphate-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), toll-like receptor 4 (TLR4), peroxisome proliferator-activated receptor γ (PPARγ) were detected by Western blotting or immunofluorescence. Results: We showed that LPS stimulated the expressions of TNF-α, IL-1β, MCP-1, VCAM-1 and TLR4, but attenuated the phosphorylation of AMPK and ACC as well as PPARγ protein levels, which were reversed by VH pretreatment. Moreover, we observed that LPS-upregulated TLR4 protein expressions were inhibited by PPARγ agonist pioglitazone, and the downregulated PPARγ expressions in response to LPS were partially restored by knockdown of TLR4. The negative regulation loop between TLR4 and PPARγ response to LPS was modulated by AMPK agonist AICAR (5-Aminoimidazole-4-carboxamide riboside or acadesine) or A769662. Conclusions: Taken together, our results suggested that VH ameliorated LPS-induced inflammatory cytokines production in endothelial cells via inhibition of TLR4 and activation of PPARγ, dependent on AMPK signalling pathway.

Increased levels of Vascular Cell Adhesion Molecule-1 (VCAM-1) and Inter-Cellular Adhesion Molecule-1 (ICAM-1) Correlate with Advanced Disease Features and Poor Survival in Newly Diagnosed Patients with Multiple Myeloma. Reduction Post-Bortezomib- and Lenalidomide-Based Regimens.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1824-1824
Author(s):  
Magdalini Migkou ◽  
Evangelos Terpos ◽  
Dimitrios Christoulas ◽  
Maria Gavriatopoulou ◽  
Georgios Boutsikas ◽  
...  
Keyword(s):  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Advanced Disease ◽  
Serum Levels ◽  
Cellular Adhesion ◽  
Newly Diagnosed ◽  
Poor Survival ◽  
Β2 Microglobulin ◽  
Cellular Adhesion Molecule ◽  
First Relapse

Abstract Abstract 1824 Poster Board I-850 Interactions between myeloma (MM) cells and bone marrow stromal cells (BMSCs) are strongly implicated in the biology of MM. The aim of this study was to evaluate the serum levels of adhesion molecules, such as VCAM-1 (CD106), ICAM-1 (CD54), P-, L- and E-selectin in patients with MM and explore possible correlations with clinical and laboratory data. The study population included 87 newly diagnosed patients (42M/45F; median age 68 years): 59 with symptomatic MM, 21 with asymptomatic MM (AMM) and 7 with MGUS, as well as 21 MM patients at first relapse (11M/10F, median age 69 years) who received the combination of bortezomib/dexamethasone (VD) and 20 MM patients at first relapse (11M/9F, median age 68.5 years) who were treated with the combination of lenalidomide plus low-dose dexamethasone (Rd). The aforementioned adhesion molecules were measured in the serum of newly-diagnosed patients before the administration of any kind of therapy, in relapsed patients on Day 1 of cycle 1 and on the last day of cycle 4 and in 43 healthy controls using ELISA method (R&D Systems, Minneapolis, MN, USA). Patients with newly-diagnosed or relapsed MM had increased levels of all studied molecules compared to controls (p<0.01), while in MGUS only serum VCAM-1 and ICAM-1 levels were elevated compared to controls (p<0.01). Newly-diagnosed patients with symptomatic MM had increased levels of VCAM-1 (mean±SD: 1168.5±810.4 ng/ml) and ICAM-1 (371.0±162.7 ng/mL) when compared to AMM patients (642.6±340.9 ng/ml, p<0.0001; and 274.4±65.5 ng/ml, p=0.002, for VCAM-1 and ICAM-1, respectively) and to MGUS patients (629.8±228.5 ng/ml, p=0.012; and 247.9±53.9, p=0.009, for VCAM-1 and ICAM-1, respectively). Furthermore, newly-diagnosed symptomatic MM had increased levels of E-selectin (43.2±20.0 ng/ml) compared to AMM (33.6±16.6 ng/ml, p=0.047). VCAM-1 was lower in patients with ISS-1 (768.2±225.1 ng/ml) compared to patients with ISS-2 (1121.7±991.2 ng/ml) and ISS-3 (1456.8±785.7 ng/ml; ANOVA p=0.04), while P-selectin was higher in ISS-1 (172.7±76.6 ng/ml) compared to ISS-2 (118.7±75.5 ng/ml) and ISS-3 MM (108.3±76.4; ANOVA p=0.042). For all newly-diagnosed patients, there was a strong correlation between VCAM-1 and ICAM-1 (r=0.598, p<0.0001). Serum VCAM-1 showed strong positive correlations with β2-microglobulin (r=0.564, p<0.0001), urea (r=0.384, p=0.001) and creatinine (r=0.376, p=0.001) and negative correlation with Hb (r=-0.346, p=0.002). Similarly, ICAM-1 positively correlated with β2-microglobulin (r=0.340, p=0.003), creatinine (r=0.290, p=0.01) and urea (r=0.254, p=0.025), and negatively correlated with Hb (r=-0.237, p=0.037). Serum P-selectin positively correlated with platelet counts (r=0.555, p<0.0001), Hb (r=0.416, p<0.0001) and albumin (r=0.270, p=0.017), but negatively correlated with β2-microglobulin (r=-0.383; p=0.001) and creatinine (r=-0.294, p=0.009). For L-selectin there was a positive correlation with albumin (r=0.370; p=0.001). The median follow-up of patients with newly-diagnosed symptomatic MM was 22 months (range: 4-54 months) and the median OS was 42 months. Increased levels of VCAM-1, ICAM-1 and L-selectin predicted for inferior survival. In particular, patients with VCAM-1 >1358.5 ng/ml had a median OS of 20 months in comparison to 42 months of all others (p=0.006), while patients with elevated ICAM-1 (>400.6 ng/ml) had a median OS of 13 months compared to 42 months of all others (p<0.0001) and patients with L-selectin >928.2 ng/ml had a median OS of 23 months compared to 42 months of all others (p=0.024). MM patients at first relapse had increased levels of VCAM-1 and ICAM-1 even compared to newly-diagnosed symptomatic MM patients (p<0.01). Both BD and Rd administration reduced dramatically serum VCAM-1 and ICAM-1 after 4 cycles of therapy (p<0.01 for all comparisons) but had no effect on the levels of selectins. The reduction of VCAM-1 and ICAM-1 was more pronounced in responders than in non-responders (p=0.032). In conclusion, patients with newly diagnosed MM have increased serum levels of VCAM-1 and ICAM-1 that correlate with advanced disease features and poor survival suggesting an important role in the biology of the disease. Selectins seem also to participate in MM pathogenesis. The administration of novel agents such as bortezomib and lenalidomide resulted in the reduction of VCAM-1 and ICAM-1 and supports a direct effect on the adhesion of MM cells to BMSCs. Disclosures No relevant conflicts of interest to declare.

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