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Background: Chronic stress is associated with activation of the HPA axis, elevation in pro‐inflammatory cytokines, decrease in intestinal epithelial cell tight junction (TJ) proteins, and enhanced visceral pain. It is unknown whether epigenetic regulatory pathways play a role in chronic stress–induced intestinal barrier dysfunction and visceral hyperalgesia. Methods: Young adult male rats were subjected to water avoidance stress ± H3K9 methylation inhibitors or siRNAs. Visceral pain response was assessed. Differentiated Caco‐2/BBE cells and human colonoids were treated with cortisol or IL‐6 ± antagonists. Expression of TJ, IL‐6, and H3K9 methylation status at gene promoters was measured. Transepithelial electrical resistance and FITC‐dextran permeability were evaluated. Key Results: Chronic stress induced IL‐6 up‐regulation prior to a decrease in TJ proteins in the rat colon. The IL‐6 level inversely correlated with occludin expression. Treatment with IL‐6 decreased occludin and induced visceral hyperalgesia. Chronic stress and IL‐6 increased H3K9 methylation and decreased transcriptional GR binding to the occludin gene promoter, leading to down‐regulation of protein expression and increase in paracellular permeability. Intrarectal administration of a H3K9 methylation antagonist prevented chronic stress–induced visceral hyperalgesia in the rat. In a human colonoid model, cortisol decreased occludin expression, which was prevented by the GR antagonist RU486, and IL‐6 increased H3K9 methylation and decreased TJ protein levels, which were prevented by inhibitors of H3K9 methylation. Conclusions & Inferences: Our findings support a novel role for methylation of the repressive histone H3K9 to regulate chronic stress, pro‐inflammatory cytokine–mediated reduction in colon TJ protein levels, and increase in paracellular permeability and visceral hyperalgesia. [ABSTRACT FROM AUTHOR]

Colon crypts are recognized as a mechanical and biochemical Turing patterning model. Colon epithelial Caco‐2 cell monolayer demonstrated 2D Turing patterns via force analysis of apical tight junction live cell imaging which illuminated actomyosin meshwork linking the actomyosin network of individual cells. Actomyosin forces act in a mechanobiological manner that alters cell/nucleus/tissue morphology. We observed the rotational motion of the nucleus in Caco‐2 cells that appears to be driven by actomyosin during the formation of a differentiated confluent epithelium. Single‐ to multi‐cell ring/torus‐shaped genomes were observed prior to complex fractal Turing patterns extending from a rotating torus centre in a spiral pattern consistent with a gene morphogen motif. These features may contribute to the well‐described differentiation from stem cells at the crypt base to the luminal colon epithelium along the crypt axis. This observation may be useful to study the role of mechanogenomic processes and the underlying molecular mechanisms as determinants of cellular and tissue architecture in space and time, which is the focal point of the 4D nucleome initiative. Mathematical and bioengineer modelling of gene circuits and cell shapes may provide a powerful algorithm that will contribute to future precision medicine relevant to a number of common medical disorders. [ABSTRACT FROM AUTHOR]

The effect of three major influence process parameters, carbon addition ratio, ore particle size, and coal particle size on the compressive strength of high-alumina iron ore-coal composite hot briquette (Al-CCB) with the application of response surface methodology is investigated in this paper. The results show that, with using multiple regression analysis, the experimental data can be fitted into a quadratic polynomial model. Based on the coefficient of determination ( R2 = 0.9883) and the analysis of variance (ANOVA), the model shows good agreement with the experimental data. The effect on the compressive strength of Al-CCB from big to small is carbon addition ratio, ore particle size, and coal particle size. In order to obtain the Al-CCB with 600 N of compressive strength, the optimal experiment conditions are found to be the coal addition ratio of 16.44%, ore particle size of −100 mesh and coal particle size of −100 mesh, resulting in an actual compressive strength of 613 N, as compared to the model prediction of 600 N. This paper can provide guidance for the optimization on preparation of Al-CCB. Also, it can offer reference for the process improvement of other ore-coal composite agglomerates. [ABSTRACT FROM AUTHOR]

Long noncoding RNA SPRY4‐IT1 has been reported to promote melanoma cell growth and invasion, and to block apoptosis. The purpose of this study was to investigate the clinical significance of SPRY4‐IT1 in patients with malignant melanoma. The relative expression levels of SPRY4‐IT1 were measured in plasma samples from 70 patients and 79 healthy controls by quantitative reverse transcriptase polymerase chain reaction. SPRY4‐IT1 expression is high in melanoma patients but low in healthy controls, and is closely associated with tumor site and tumor stage. Elevated SPRY4‐IT1 significantly reduces overall survival rates of patients and is considered as an independent prognostic factor in patients with melanoma. The prognostic nomogram shows a good prediction of the probability of 5‐year overall survival of patients with melanoma (c‐index: 0.72). The calibration curve for the probability of survival presents good agreement between actual outcomes and predictive consequences. In summary, SPRY4‐IT1 may be a potential prognostic marker and a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Background and Purpose: Cryptotanshinone (CTS) is a major bioactive diterpenoid isolated from Danshen, an eminent medicinal herb that is used to treat cardiovascular disorders in Asian medicine. However, it is not known whether CTS can prevent experimental atherosclerosis. The present study was designed to investigate the protective effects of CTS on atherosclerosis and its molecular mechanisms of action.Experimental Approach: Apolipoprotein E-deficient (ApoE(-/-)) mice, fed an atherogenic diet, were dosed daily with CTS (15, 45 mg kg(-1) day(-1)) by oral gavage. In vitro studies were carried out in oxidized LDL (oxLDL)-stimulated HUVECs treated with or without CTS.Key Results: CTS significantly attenuated atherosclerotic plaque formation and enhanced plaque stability in ApoE(-/-) mice by inhibiting the expression of lectin-like oxLDL receptor-1 (LOX-1) and MMP-9, as well as inhibiting reactive oxygen species (ROS) generation and NF-κB activation. CTS treatment significantly decreased the levels of serum pro-inflammatory mediators without altering the serum lipid profile. In vitro, CTS decreased oxLDL-induced LOX-1 mRNA and protein expression and, thereby, inhibited LOX-1-mediated adhesion of monocytes to HUVECs, by reducing the expression of adhesion molecules (intracellular adhesion molecule 1 and vascular cellular adhesion molecule 1). Furthermore, CTS inhibited NADPH oxidase subunit 4 (NOX4)-mediated ROS generation and consequent activation of NF-κB in HUVECs.Conclusions and Implications: CTS was shown to have anti-atherosclerotic activity, which was mediated through inhibition of the LOX-1-mediated signalling pathway. This suggests that CTS is a vasculoprotective drug that has potential therapeutic value for the clinical treatment of atherosclerotic cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Coxsackievirus B3 (CVB3), an important human causative pathogen for viral myocarditis, pancreatitis, and meningitis, has evolved different strategies to manipulate the host signaling machinery to ensure successful viral infection. We previously revealed a crucial role for the ERK1/2 signaling pathway in regulating viral infectivity. However, the detail mechanism remains largely unknown. Grb2-associated binder 1 (GAB1) is an important docking protein responsible for intracellular signaling assembly and transduction. In this study, we demonstrated that GAB1 was proteolytically cleaved after CVB3 infection at G175 and G436 by virus-encoded protease 2Apro, independent of caspase activation. Knockdown of GAB1 resulted in a significant reduction of viral protein expression and virus titers. Moreover, we showed that virus-induced cleavage of GAB1 is beneficial to viral growth as the N-terminal proteolytic product of GAB1 (GAB1-N1-174) further enhances ERK1/2 activation and promotes viral replication. Our results collectively suggest that CVB3 targets host GAB1 to generate a GAB1-N1-174 fragment that enhances viral infectivity, at least in part, via activation of the ERK pathway. The findings in this study suggest a novel mechanism that CVB3 employs to subvert the host signaling and facilitate consequent viral replication. [ABSTRACT FROM AUTHOR]

The objective of this study was to establish a quantitative method to evaluate the biotransportation of a drug across the cell membrane. Through the application of the law of mass conservation, the drug transportation rate was calculated based on Fick's law of passive diffusion and the Michaelis-Menten equation. The overall membrane-transportation rate was the sum of the passive diffusion rate and the carrier-mediated diffusion rate, which were calculated as the transportation mass divided by the respective rate. The active ingredients of Puerariae lobatae Radix and Chuanxiong rhizoma, namely, puerarin and ferulic acid, respectively, were used as two model drugs. The transportation rates of puerarin and ferulic acid were obtained by fitting a model that includes both Fick's law of diffusion and the Michaelis-Menten equation. Compared with the overall transportation, the carrier-mediated transport and passive diffusion of 1.59 mmol/L puerarin were -35.07% and 64.93%, respectively, whereas the respective transportation modes of 0.1 mmol/L ferulic acid were -35.40% and 64.60%, respectively. Verapamil and MK-571 increased the overall transport rate and ratio, and MK-571 treatment changed the carrier-mediated transport from negative to positive. However, the transport rate and ratio of ferulic acid did not change significantly. The cell transportation mechanisms of puerarin and ferulic acid primarily involve simple passive diffusion and carrier-mediated transportation. Moreover, P-glycoprotein and multidrug resistance-associated protein efflux proteins, and other transportation proteins were found to be involved in the transportation of puerarin. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Radix Angelicae Dahuricae is the dried root of Angelicae Dahurica (Fisch.ex Hoffm.)Benth.et Hook.f. var. formosana (Boiss.) Shan et Yuan (Fam.Umbelliferae). The total coumarins (Cou) and volatile oil (VO) were main active components that drived from Radix Angelicae Dahuricae. Our previous studies have shown that Cou and VO could increase intestinal absorption for transmucosal drug delivery with unknown mechanism. The aim of this study was to investigate the molecular mechanism of Radix Angelicae Dahuricae for improving drug intestinal transport. Caco-2 cell model was used to study the effect of Radix Angelicae Dahurica on transepithelial electrical resistance. Western blot was used to study its effect on the expression of the actin and ZO-1, tight junction proteins. The effect of Radix Angelicae Dahurica on the expression of P-gp protein was investigated using flow cytometry. VO (0.036-2.88 μL/mL) and Cou (0.027-0.54 mg/mL) caused a reversible, time- and dose-dependent decrease in transepithelial electrical resistance. VO and/or Cou could inhibit the expression of the tight junction protein, ZO-1 and actin. VO and/or Cou also could inhibit the expression of P-gp. These data suggested that Radix Angelicae Dahurica increased cell permeability by affecting the expression of actin, ZO-1 or P-gp, opening the tight junction or inhibiting the efflux induced by P-gp. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The root of Angelica dahurica (Radix Angelicae Dahuricae, RAD), which contains coumarins and volatile oil as its main classes of active components, is often given in conjunction with Pueraria root (Radix Puerariae, RP), which contains the phytoestrogen puerarin. The two herbs are considered to be compatible 'herb-pairs' in traditional Chinese medicine. The present investigation investigates the absorption of puerarin from RP and the effect of the total coumarins and volatile oil from RAD on its absorption. The everted gut sac and single-pass intestinal perfusion methods were used, respectively. The results showed that the absorption of puerarin in the jejunum was significantly increased in the presence of the coumarins and/or volatile oil. The absorption rate constant (Ka) of puerarin increased gradually until the concentration reached 160 µg · mL−1, after which its absorption became saturated and the apparent permeability (Papp) values significantly decreased. The results showed that the intestinal absorption mechanisms of puerarin involved active transportation processes and that puerarin is likely to be a substrate of P-gp because verapamil significantly affected its Papp and Ka. The absorption of puerarin significantly increased ( p < 0.01) when combined with RAD extracts, as shown by the increase in concentration of puerarin in blood from the hepatic portal vein, supporting the concept of RAD and RP as a compatible herb-pair. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Blast furnace operation with natural gas (NG) injection is one of the effective measures to save energy, reduce CO2 emission, and decrease environmental load for iron and steel industry. Numerical simulations on blast furnace operation with NG injection through tuyeres are performed in this paper by raceway mathematical model, multi-fluid blast furnace model, and exergy analytical model. With increasing NG injection volume, the simulation results are shown as follows: (1) the theoretical flame temperature and bosh gas volume can be constant by decreasing blast volume and increasing oxygen enrichment. (2) The utilization rate of CO enhances while that of H2 decreases. The proportion of H2 in indirect reduction tends to be increased, which accelerates the reduction of burdens. The pressure drop shows that the permeability of blast furnace gets better. The blast furnace productivity is increased from 2.07 to 3.08 t · m−3 · day−1. The silicon content in hot metal is decreased from 0.26% to 0.05%. When BF operation with 125.4 kg · tHM−1 NG injection, coke rate and carbon emission rate are decreased by 27.2% and 32.2%, respectively. (3) The thermodynamic perfection degree is increased from 88.40% to 90.50%, the exergy efficiency is decreased from 51.94% to 49.02% and the chemical exergy of top gas is increased from 4.69 to 6.22 GJ · tHM−1. It is important to strengthen the recycling of top gas. [ABSTRACT FROM AUTHOR]

To extract, preconcentrate and determine the trace level of environmental contaminants, a novel mixed hemimicelles solid-phase extraction (MHSPE) method based on mesoporous silica-coated magnetic nanoparticles (Fe3O4/meso-SiO2 NPs) as adsorbent was developed for extraction of phthalate esters from water samples. The Fe3O4/meso-SiO2 NPs were synthesized by using a combination of hydrothermal method and sol-gel method. The obtained Fe3O4/meso-SiO2 NPs possessed a large surface area (570 m2/g), superparamagnetism, and uniform mesopores (2.8 nm). MHSPE parameters, such as the amount of surfactant, pH of sample, shaking and separation time, eluent and breakthrough volume that may influence the extraction of analytes greatly, were further investigated. Under the optimized conditions, the extraction was completed in 20 min and a concentration factor of 500 was achieved by extracting 250 mL water sample. Detection limits obtained of butyl-benzyl phthalate (BBP), di-n-butyl phthalate (DnBP), di-(2-ethylhexyl) phthalate (DEHP) and di-n-cotyl phthalate (DnOP) were 12, 21, 12, and 32 ng/L, respectively. The proposed method exhibited high extraction efficiency and relatively short time for extracting the target compounds. [ABSTRACT FROM AUTHOR]

Carbon composite iron ore hot briquette (CCB) is the product of fine iron ore and fine coal by hot briquetting process, which attracts more and more attention as a new type of ironmaking raw materials aiming to improve the operation efficiency and reduce the coke consumption of blast furnace. This paper is devoted to experimental study on metallurgical properties of CCB and numerical simulation of the BF operation with CCB charging. At first, the metallurgical properties of CCB, including cold crushing strength, RDI, RSI, reducibility, high temperature strength, and softening and dripping are experimentally tested and compared with the common burdens, which revealed that the CCB possesses the required metallurgical properties and is suitable to use as the blast furnace burden. Then, the effects of charging CCB on the dripping properties of comprehensive burdens are elucidated based on the experiments under simulated blast furnace conditions. The results showed that the maximum charging ratio of CCB in the iron burdens is 40%-50% for achieving appropriate dripping properties of the mixed burdens. Finally, a multi-fluid blast furnace model is used to simulate BF operation with CCB charging. According to model simulations, charging CCB will cause the temperature level to decreases in the furnace and the location of the cohesive zone shifts downward. On the other hand, the productivity tends to increase while coke rate and total reducing agent rate decrease, the heat efficiency improves remarkably and the operation performance of BF is effectively enhanced. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor (VEGF) induces phosphorylation of VEGF receptor-2 (VEGFR-2) and activates the downstream signaling pathway resulting in endothelial cell migration, proliferation, and survival. Cigarette smoking is associated with abnormal vascular and endothelial function, leading to airspace enlargement. Herein, we investigated the mechanism of cigarette smoke (CS) -induced endothelial dysfunction by studying the VEGF-VEGFR-2 signaling in mouse lung and human endothelial cells. CS exposure caused oxidative stress, as shown by increased levels of 4-hydroxy-2-n0nenal-adducts in mouse lung and reactive oxygen species generation in human lung microvascular endothelial cells (HMVEC-Ls). Inhibition of VEGFR-2 by a specific kinase inhibitor (NVP-AAD777) enhanced the CS-induced oxidative stress, causing augmented inflammatory cell influx and proinflammatory mediators release in mouse lung. The levels of endothelial nitric oxide synthase (eNOS) and phosphorylated (p) -eNOS in the lungs of mice exposed to CS and/or treated with VEGFR-2 inhibitor were decreased. CS down-regulated VEGFR-2 expression, eNOS levels, and VEGF-induced VEGFR-2 phosphorylation in HMVEC-Ls, resulting in impaired VEGF-induced endothelial cell migration and angiogenesis. Overall, these data show that inhibition of VEGFR-2 augmented CS-induced oxidative stress and inflarmnatory responses leading to endothelial dysfunction. This explains the mechanism of endothelial dysfunction in smokers and has implications in understanding the pathogenesis of pulmonary and cardiovascular diseases.--Edirisinghe, I., Yang, S.-E., Yao, H., Rajendrasozhan, S., Caito, S., Adenuga, D., Wong, C., Rahman, A., Phipps, R. P., Jin, Z.-G., Rahman, I. VEGFR-2 inhibition augments cigarette smoke-induced oxidative stress and inflammatory responses leading to endothelial dysfunction. [ABSTRACT FROM AUTHOR]

Until 30 years ago, it had been considered that D-amino acids were excluded from living systems except for D-amino acids in the cell wall of microorganisms. However, D-amino acids, in the form of free amino acids, peptides and proteins, were recently detected in various living organisms from bacteria to mammals. The extensive distribution of bio-functional D-amino acids challenges the current concept of protein synthesis: more attention should be paid to the stereospecificity of the translation machine. Besides aminoacyl-tRNA synthetases, elongation factor Tu and some other mechanisms, D-Tyr-tRNATyr deacylases provide a novel checkpoint since they specifically recycle misaminoacylated D-Tyr-tRNATyr and some other D-aminoacyl-tRNAs. Their unique structure represents a new class of tRNA-dependent hydrolase. These unexpected findings have far-reaching implications for our understanding of protein synthesis and its origin. [Copyright &y& Elsevier]

Background: Chronic psychological stress is associated with increased intestinal epithelial permeability and visceral hyperalgesia. Lubiprostone, an agonist for chloride channel‐2, promotes secretion and accelerates restoration of injury‐induced epithelial barrier dysfunction. The mechanisms underlying how lubiprostone regulates colon epithelial barrier function and visceral hyperalgesia in chronic stress remain unknown. Methods: Male rats were subjected to water avoidance stress for 10 consecutive days. Lubiprostone was administered daily during the stress phase. Visceromotor response to colorectal distension was measured. Human colon crypts and cell lines were treated with cortisol and lubiprostone. The transepithelial electrical resistance and FITC‐dextran permeability were assayed. Chromatin immunoprecipitation was conducted to assess glucocorticoid receptor binding at tight junction gene promoters. Key Results: Lubiprostone significantly decreased chronic stress‐induced visceral hyperalgesia in the rat (P < 0.05; n = 6). WA stress decreased occludin and claudin‐1 and increased claudin‐2 in rat colon crypts, which was prevented by lubiprostone. Cortisol treatment induced similar alterations of tight junction protein expression in Caco‐2/BBE cells (P < 0.05) and significantly changed paracellular permeability in monolayers (P < 0.01). These changes were blocked by lubiprostone. Glucocorticoid receptor and its binding at occludin promoter region were decreased in cortisol‐treated cells and human colon crypts, which was largely reversed by lubiprostone. In rat colonic cells, glucocorticoid receptor and its co‐chaperone proteins were down‐regulated after corticosterone treatment and lubiprostone reversed these changes. Conclusions & Inferences: Lubiprostone preferentially prevents chronic stress‐induced alterations of intestinal epithelial tight junctions, barrier function, and visceral hyperalgesia that was associated with modulation of glucocorticoid receptor expression and function. Lubiprostone preferentially prevents chronic stress‐induced alterations of intestinal epithelial tight junctions, barrier function, and visceral hyperalgesia that was associated with modulation of glucocorticoid receptor expression and function. [ABSTRACT FROM AUTHOR]

Oxadiazoles (II) are synthesized by anodic oxidation of benzoyl hydrazines (I). [ABSTRACT FROM AUTHOR]

Angiotensin II (Ang II) induces the phenotypic modulation and hypertrophy of vascular smooth muscle cells (VSMCs), which is implicated in the pathogenesis of hypertension and atherosclerosis. Here we established a novel role of histone deacetylases 5 (HDAC5) in Ang II-induced VSMC hypertrophy. We showed that Ang II rapidly stimulated phosphorylation of HDAC5 (p-HDAC5) on Ser259/498 sites in a time- and dose- dependent manner in rat aortic VSMCs. Ang II receptor 1 mediated p-HDAC5. Protein kinase C (PKC) inhibitors, GF109203X and Gö6983, inhibited p-HDAC5. Using pharmacological inhibitor, siRNA and adenovirus encoding kinase-negative mutant of protein kinase D (PKD) demonstrated that PKD was essential for p-HDAC5 by Ang II. Moreover, we showed that Ang II stimulated HDAC5 nuclear export, which was dependent on its phosphorylation via PKC/PKD pathway, because HDAC5 nuclear export was abolished by inhibiting PKC and PKD and by infection of adenovirus encoding HDAC5 S259/498A mutant. Furthermore, both PKD inhibition and HDAC5 S259/498A mutant blocked Ang II-induced myocyte enhancer factor 2 (MEF2) transcriptional activation. Importantly, Ang II promoted VSMC protein synthesis in PKD and HDAC5-dependent manner. Our findings reveal for the first time that PKD and HDAC5 play a key role in Ang II-induced VSMC hypertrophy, and suggest that PKD and HDAC5 may emerge as potential targets for cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor (VEGF) is essential for many angiogenic processes. Histone deacetylases (HDACs) have emerged as key transcriptional regulators. Here we showed that VEGF induced Protein kinase D (PKD)-dependent HDAC5 phosphorylation and nuclear export in endothelial cells. VEGF rapidly, stimulated HDAC5 phosphorylation (p-HDAC5) at Ser259/498 residues in a time- and dose-dependent manner in bovine aortic endothelial cells and human umbilical vein endothelial cells. VEGF-induced p-HDAC5 was mediated via VEGF receptor 2, phospholipase Cγ (PLCγ), protein kinase C (PKC) and PKD pathway. Specifically, PLCγ and PKCs inhibitors diminished p-HDAC5. Inhibiting PKD by siRNA and adenovirus encoding kinase-negative mutant blocked p-HDACS. Furthermore, VEGF stimulated nuclear export of HDAC5 in a phosphorylation-dependent manner, which leads to myocyte enhance factors-2 (MEF2) transcriptional activation. Active PKD stimulated HDAC5 nuclear export and MEF2 activation. In contrast, inhibiting PKD prevented VEGF-mediated HDAC5 nuclear export and MEF2 activation. Moreover, adenovirus encoding HDAC5 S258/498A mutant abolished VEGF-mediated HDAC5 nuclear export and MEF2 activation. Our findings reveal a novel role of PKD and HDAC5 in VEGF regulation of gene transcription and suggest that PKD and HDAC5 may emerge as potential therapeutic targets for pathological angiogenesis. [ABSTRACT FROM AUTHOR]

Background: Kruppel-like factor 2 (KLF2) is an important zinc-finger transcription factor that maintains endothelial homeostasis by its anti-inflammatory, -thrombotic, -oxidative, and -proliferative effects in endothelial cells. In light of the potent vasoprotective effects of KLF2, modulating KLF2 expression or function could give rise to new therapeutic strategies to treat cardiovascular diseases., Methods and Results: High-throughput drug screening based on KLF2 promoter luciferase reporter assay was performed to screen KLF2 activators. Real-time PCR and western blot were used to detect gene and protein expression. Identified KLF2 activator was orally administered to ApoE -/- mice to evaluate anti-atherosclerotic efficacy. By screening 2400 compounds in the Spectrum library, we identified suberanilohydroxamic (SAHA) acid, also known as vorinostat as a pharmacological KLF2 activator through myocyte enhancer factor 2. We found that SAHA exhibited anti-inflammatory effects and attenuated monocyte adhesion to endothelial cells inflamed with tumor necrosis factor alpha. We further showed that the inhibitory effect of SAHA on endothelial inflammation and ensuing monocyte adhesion was KLF2 dependent using KLF2-deficient mouse lung endothelial cells or KLF2 small interfering RNA- depleted human endothelial cells. Importantly, we observed that oral administration of SAHA reduced diet-induced atherosclerotic lesion development in ApoE -/- mice without significant effect on serum lipid levels., Conclusions: These results demonstrate that SAHA has KLF2-dependent anti-inflammatory effects in endothelial cells and provide the proof of concept that KLF2 activation could be a promising therapeutic strategy for treating atherosclerosis., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)