scholarly journals Tetrahydroxystilbene Glucoside Protects Against Oxidized LDL-Induced Endothelial Dysfunction via Regulating Vimentin Cytoskeleton and its Colocalization with ICAM-1 and VCAM-1

2014 ◽  
Vol 34 (5) ◽  
pp. 1442-1454 ◽  
Author(s):  
Wenjuan Yao ◽  
Chao Huang ◽  
Qinju Sun ◽  
Xiang Jing ◽  
Huiming Wang ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Oxidized Ldl ◽  
Tetrahydroxystilbene Glucoside

Abstract 166: Endothelial Overexpression of LOX-1 Increases Stroke Size in vivo

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Alexander Akhmedov ◽  
Remo D Spescha ◽  
Francesco Paneni ◽  
Giovani G Camici ◽  
Thomas F Luescher
Keyword(s):  
Endothelial Cells ◽  
Ischemic Stroke ◽  
Endothelial Dysfunction ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Oxidized Ldl ◽  
Artery Occlusion ◽  
Cerebral Artery Occlusion ◽  
The Brain

Background— Stroke is one of the most common causes of death and long term disability worldwide primarily affecting the elderly population. Lectin-like oxidized LDL receptor 1 (LOX-1) is the receptor for oxidized LDL identified in endothelial cells. Binding of OxLDL to LOX-1 induces several cellular events in endothelial cells, such as activation of transcription factor NF-kB, upregulation of MCP-1, and reduction in intracellular NO. Accumulating evidence suggests that LOX-1 is involved in endothelial dysfunction, inflammation, atherogenesis, myocardial infarction, and intimal thickening after balloon catheter injury. Interestingly, a recent study demonstrated that acetylsalicylic acid (aspirin), which could prevent ischemic stroke, inhibited Ox-LDL-mediated LOX-1 expression in human coronary endothelial cells. The expression of LOX-1 was increased at a transient ischemic core site in the rat middle cerebral artery occlusion model. These data suggest that LOX-1 expression induces atherosclerosis in the brain and is the precipitating cause of ischemic stroke. Therefore, the goal of the present study was to investigate the role of endothelial LOX-1 in stroke using experimental mouse model. Methods and Results— 12-week-old male LOX-1TG generated recently in our group and wild-type (WT) mice were applied for a transient middle cerebral artery occlusion (MCAO) model to induce ischemia/reperfusion (I/R) brain injury. LOX-1TG mice developed 24h post-MCAO significantly larger infarcts in the brain compared to WT (81.51±8.84 vs. 46.41±10.13, n=7, p < 0.05) as assessed morphologically using Triphenyltetrazolium chloride (TTC) staining. Moreover, LOX-1TG showed higher neurological deficit in RotaRod (35.57±8.92 vs. 66.14±10.63, n=7, p < 0.05) and Bederson tests (2.22±0.14 vs. 1.25±0.30, n=9-12, p < 0.05) - two experimental physiological tests for neurological function. Conclusions— Thus, our data suggest that LOX-1 plays a critical role in the ischemic stroke when expressed at unphysiological levels. Such LOX-1 -associated phenotype could be due to the endothelial dysfunction. Therefore, LOX-1 may represent novel therapeutic targets for preventing ischemic stroke.

scholarly journals The reciprocal relationship between adiponectin and LOX-1 in the regulation of endothelial dysfunction in ApoE knockout mice

2010 ◽  
Vol 299 (3) ◽  
pp. H605-H612 ◽  
Author(s):  
Xiuping Chen ◽  
Hanrui Zhang ◽  
Steve McAfee ◽  
Cuihua Zhang
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Sodium Nitroprusside ◽  
Oxidized Ldl ◽  
Reciprocal Relationship ◽  
Reciprocal Regulation ◽  
Tnf Α ◽  
Ldl Uptake ◽  
Apoe Ko Mice ◽  
Apoe Ko

We hypothesized that the reciprocal association between adiponectin and lectin-like oxidized LDL (ox-LDL) receptor (LOX)-1 contributes to the regulation of aortic endothelial dysfunction in atherosclerosis. To test this hypothesis, endothelium-dependent (ACh) and endothelium-independent (sodium nitroprusside) vasorelaxation of isolated aortic rings from control mice, apolipoprotein E (ApoE) knockout (KO) mice, and ApoE KO mice treated with either adiponectin (15 μg·day−1·mouse−1 sc for 8 days) or neutralizing antibody to LOX-1 (anti-LOX-1, 16 μg/ml, 0.1 ml/mouse ip for 7 days) were examined. Although vasorelaxation to sodium nitroprusside was not different between control and ApoE KO mice, relaxation to ACh was impaired in ApoE KO mice. Adiponectin and anti-LOX-1 restored nitric oxide-mediated endothelium-dependent vasorelaxation in ApoE KO mice. Aortic ROS formation and ox-LDL uptake were increased in ApoE KO mice. Both adiponectin and anti-LOX-1 treatment reduced ROS production and aortic ox-LDL uptake. In mouse coronary artery endothelial cells, TNF-α incubation increased endothelial LOX-1 expression. Adiponectin reduced TNF-α-induced LOX-1 expression. Consistently, in ApoE KO mice, adiponectin treatment reversed elevated LOX-1 expression in aortas. Immunofluorescence staining showed that adiponectin was mainly colocalized with endothelial cells. Although adiponectin expression was lower in ApoE KO versus control mice, anti-LOX-1 increased aortic adiponectin expression, suggesting a reciprocal regulation between adiponectin and LOX-1. Moreover, both adiponectin and anti-LOX-1 reduced NF-κB expression in ApoE KO mice. Thus, adiponectin and LOX-1 may converge on NF-κB signaling to regulate their function. In conclusion, our results indicate that the reciprocal regulation between adiponectin and LOX-1 amplifies oxidative stress and ox-LDL uptake, leading to endothelial dysfunction in atherosclerosis.

scholarly journals Role of Lectin-Like Oxidized Low Density Lipoprotein-1 in Fetoplacental Vascular Dysfunction in Preeclampsia

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Felipe A. Zuniga ◽  
Valeska Ormazabal ◽  
Nicolas Gutierrez ◽  
Valeria Aguilera ◽  
Claudia Radojkovic ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Vascular Dysfunction ◽  
Pathological Condition ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Fetal Loss ◽  
Density Lipoprotein ◽  
Placental Tissue

The bioavailability of nitric oxide (NO) represents a key marker in vascular health. A decrease in NO induces a pathological condition denominated endothelial dysfunction, syndrome observed in different pathologies, such as obesity, diabetes, kidney disease, cardiovascular disease, and preeclampsia (PE). PE is one of the major risks for maternal death and fetal loss. Recent studies suggest that the placenta of pregnant women with PE express high levels of lectin-like oxidized LDL receptor-1 (LOX-1), which induces endothelial dysfunction by increasing reactive oxygen species (ROS) and decreasing intracellular NO. Besides LOX-1 activation induces changes in migration and apoptosis of syncytiotrophoblast cells. However, the role of this receptor in placental tissue is still unknown. In this review we will describes the physiological roles of LOX-1 in normal placenta development and the potential involvement of this receptor in the pathophysiology of PE.

Combination Eicosapentaenoic Acid and Statin Treatment Reversed Endothelial Dysfunction in HUVECs Exposed to Oxidized LDL

2014 ◽  
Vol 8 (3) ◽  
pp. 342-343 ◽  
Author(s):  
R. Preston Mason ◽  
Robert F. Jacob ◽  
J. Jose Corbalan ◽  
Tadeusz Malinski
Keyword(s):  
Endothelial Dysfunction ◽  
Eicosapentaenoic Acid ◽  
Oxidized Ldl ◽  
Statin Treatment

scholarly journals Thrombomodulin as a New Marker of Endothelial Dysfunction in Chronic Kidney Disease in Children

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Dorota Drożdż ◽  
Monika Łątka ◽  
Tomasz Drożdż ◽  
Krystyna Sztefko ◽  
Przemko Kwinta
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Cystatin C ◽  
Oxidized Ldl ◽  
Left Ventricular ◽  
Intercellular Adhesion Molecule ◽  
Oxidative Stress Biomarkers ◽  
Ckd Stage

Endothelial dysfunction (ED) and oxidative stress are potential new pathomechanisms of cardiovascular diseases in patients with chronic kidney disease (CKD). The aim of the study was to assess the association between endothelial dysfunction, oxidative stress biomarkers, and cardiovascular risk factors in children with CKD. Serum oxidized LDL (oxLDL), protein carbonyl group, urea, creatinine, cystatin C, thrombomodulin, asymmetric dimethylarginine (ADMA), von Willebrand factor, brain natriuretic peptide (BNP), lipids, high sensitivity C-reactive protein, intercellular adhesion molecule-1 levels, and albuminuria were measured. Anthropometric, ambulatory blood pressure (BP) measurements and echocardiography were performed. The studied group consisted of 59 patients aged 0.7–18.6 (mean 11.1) years with stages 1 to 5 CKD. Thrombomodulin strongly correlated with creatinine (R=0.666; p<0.001), cystatin C (R=0.738; p<0.001), BNP (R=0.406; p=0.001), ADMA (R=0.353; p=0.01), oxLDL (R=0.340; p=0.009), 24-hour systolic (R=0.345; p=0.011) and mean (R=0.315; p<0.05) BP values, and left ventricular mass index (LVMI, R=0.293; p=0.024) and negatively with estimated glomerular filtration rate (R=−0.716; p<0.001). In children with CKD, TM strongly depended on kidney function parameters, oxLDL levels, and 24-hour systolic and mean BP values. Thrombomodulin seems to be a valuable marker of ED in CKD patients, correlating with CKD stage as well as oxidative stress, BP values, and LVMI.

scholarly journals The Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 and Cardiovascular Disease

1970 ◽  
Vol 3 (2) ◽  
pp. 169-177
Author(s):  
MSA Sheikh ◽  
T Yang ◽  
U Salma ◽  
M Ali
Keyword(s):  
Signal Transduction ◽  
Endothelial Dysfunction ◽  
Morphological Changes ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Soluble Form ◽  
Low Density ◽  
Coronary Syndrome

Lectin-like oxidized LDL receptor-1 (LOX-1), a lectin-like 50-kD receptor for oxidized low-density lipoproteins (ox-LDL), is present primarily on endothelial cells. Oxidatively modified low-density lipoprotein (oxLDL) is implicated in the pathogenesis of atherosclerosis. Endothelial dysfunction is the initial change in the vascular wall that induces morphological changes for atheroma-formation. LOX-1 was identified as the receptor for oxLDL that was thought to be a major cause of endothelial dysfunction. LOX-1 has been demonstrated to contribute not only to endothelial dysfunction, but also to atherosclerotic-plaque formation, hypertension, myocardial infarction and intimal thickening after balloon injury. Studies with transgenic and knockout mouse models have elucidated in part the role of LOX-1 in the pathogenesis of atherosclerosis and cardiac remodeling. Recently, a circulating soluble form of LOX-1(sLOx-1), corresponding solely to its extracellular domain, has been identified in human serum. Circulating levels of sLOX-1 are increased in inflammatory and atherosclerotic conditions and are associated with acute coronary syndrome, with the severity of coronary artery disease, and with serum biomarkers for oxidative stress and inflammation, suggesting that they could be useful marker for vascular injury. Identification and regulation of this receptor and understanding of signal transduction pathways might open new gateways from diagnosis to therapeutics for cardiovascular diseases. Keywords: Atherosclerosis; Endothelial dysfunction; LOX-1; ox-LDL; Signal transduction. DOI: http://dx.doi.org/10.3329/cardio.v3i2.9187 Cardiovasc. J. 2011; 3(2): 169-177

scholarly journals Soluble Lectin-Like Oxidized LDL Receptor 1 as a Possible Mediator of Endothelial Dysfunction in Patients With Metabolic Syndrome

2014 ◽  
Vol 29 (3) ◽  
pp. 184-190 ◽  
Author(s):  
S. Civelek ◽  
M. Kutnu ◽  
H. Uzun ◽  
F. Erdenen ◽  
E. Altunoglu ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Endothelial Dysfunction ◽  
Oxidized Ldl ◽  
Ldl Receptor

Tetrahydroxystilbene Glucoside Inhibits Excessive Autophagy and Improves Microvascular Endothelial Dysfunction in Prehypertensive Spontaneously Hypertensive Rats

2016 ◽  
Vol 44 (07) ◽  
pp. 1393-1412 ◽  
Author(s):  
Qianqian Dong ◽  
Wenjuan Xing ◽  
Feng Fu ◽  
Zhenghua Liu ◽  
Jie Wang ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Mesenteric Artery ◽  
Spontaneously Hypertensive Rats ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Tetrahydroxystilbene Glucoside

Autophagy exists in vascular endothelial cells, but the relationship between autophagy and blood vessel dysfunction in hypertension remains elusive. This study aimed to investigate role of autophagy in vascular endothelial dysfunction in prehypertension and hypertension and the underlying mechanisms involved. Furthermore, we sought to determine if and how tetrahydroxystilbene glucoside (TSG), a resveratrol analogue and active ingredient of Polygonum multiflorum Thunb used for its cardiovascular protective properties in traditional Chinese medicine, influences vascular endothelial function. Male spontaneously hypertensive rats (SHRs) aged 4 weeks (young) and 12 weeks (adult) were studied and the vascular function of isolated aorta and mesenteric artery was assessed in vitro. Compared with Wistar Kyoto rats (WKY), young and adult SHRs showed endothelial dysfunction of the aorta and mesenteric artery, along with decreased pAkt, pmTOR, and autophagic marker protein p62 and increased LC3 II/I in microvascular but not aortic tissues. TSG administration for 14 days significantly improved mesenteric vascular endothelial function, increased levels of pAkt and pmTOR, and decreased autophagy. Pretreatment of young SHRs with the mTOR inhibitor rapamycin blocked the antiautophagic and vasodilative effects of TSG. Moreover, TSG significantly activated Akt-mTOR signaling in HUVECs and reduced the autophagic levels in vitro, which were almost completely blocked by rapamycin. In summary, mesenteric endothelial dysfunction in prehypertensive SHRs was at least partly attributable to excessive autophagy in vascular tissues. TSG partly restored microvascular endothelial dysfunction through activating the Akt/mTOR pathway, which consequently suppressed autophagy, indicating that TSG could be potentially applied to protect vascular function against subclinical changes in prehypertension.

Metabolic syndrome increases endogenous carbon monoxide production to promote hypertension and endothelial dysfunction in obese Zucker rats

2006 ◽  
Vol 290 (3) ◽  
pp. R601-R608 ◽  
Author(s):  
Fruzsina K. Johnson ◽  
Robert A. Johnson ◽  
William Durante ◽  
Keith E. Jackson ◽  
Blake K. Stevenson ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Carbon Monoxide ◽  
Endothelial Dysfunction ◽  
Ldl Cholesterol ◽  
Oxidized Ldl ◽  
Zucker Rats ◽  
Protein Levels ◽  
Obese Zucker Rats ◽  
Oxide Synthase

Vascular heme oxygenase (HO) metabolizes heme to form carbon monoxide (CO). Increased heme-derived CO inhibits nitric oxide synthase and can contribute to hypertension via endothelial dysfunction in Dahl salt-sensitive rats. Obese Zucker rats (ZR) are models of metabolic syndrome. This study tests the hypothesis that endogenous CO formation is increased and contributes to hypertension and endothelial dysfunction in obese ZR. Awake obese ZR showed increased respiratory CO excretion, which was lowered by HO inhibitor administration [zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG) 25 μmol·kg−1·24 h−1 ip]. In awake obese ZR, chronically instrumented with femoral arterial catheters, blood pressure was elevated but was decreased by the HO inhibitor ZnDPBG. Body weight, blood glucose, glycated hemoglobin, plasma insulin, total and LDL cholesterol, oxidized LDL, and triglyceride levels were elevated in obese ZR, and, except for LDL cholesterol, were unchanged by HO inhibition. Total HO-1 protein levels were not different between lean and obese ZR aortas. In vitro experiments used isolated skeletal muscle arterioles with constant pressure and no flow, or constant midpoint, but altered endpoint pressures to establish graded levels of luminal flow. In obese ZR arterioles, responses to ACh and flow were attenuated. Acute in vitro pretreatment with an HO inhibitor, chromium mesoporphyrin, enhanced ACh and flow-induced dilation and abolished the differences between groups. Furthermore, exogenous CO prevented the restoration of flow-induced dilation by the HO inhibitor in obese ZR arterioles. These results suggest that HO-derived CO production is increased and promotes hypertension and arteriolar endothelial dysfunction in obese ZR with metabolic syndrome independent of affecting metabolic parameters.

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