Indicator Of Bioavailability Research Articles

Effect of Holding Chamber as an Add-on Device on Aerosol Delivery and Fugitive Aerosol from Different Jet Nebulizers

A new Circulaire II (holding chamber) was designed to be used with VixOne nebulizer to increase the inhalable doses reaching the patient. The aim of this study was to evaluate the efficacy of this holding chamber with VixOne nebulizer and determine its usability with other nebulizers. The aerodynamic characteristics of emitted dose of 2 ml salbutamol solution, 5000 μg/ml, were evaluated using cooled Andersen cascade impactor at inhalation flow 15 L/min. The respirable solutions were nebulized using 3JN (VixOne, NebuTech, and En full Kit) with both holding chamber and T-piece. To evaluate the pulmonary and systemic bioavailability, 12 non-smoking health subjects (6 females), > 18 years, with an average(SD) FEV1 > 90% of predicted, inhaled nebulized aerosol of 1 ml respirable solution (5000 μg salbutamol), diluted to 2 ml total volume using normal saline through the same nebulizer setting described above using normal tidal breathing. Subjects provided urine samples 30 min post-dosing (USAL0.5) as an index of pulmonary bioavailability and cumulatively collected their urine for 24 h (USAL24) as an index of systemic bioavailability. To determine the amount that would reach the patients (aerosol-emitted), subjects again inhaled 1 ml salbutamol-diluted respirable solution through the same nebulizer setting described above but with filters to capture salbutamol-emitted. Amount of salbutamol deposited in the holding chamber was significantly higher than in T-piece among all nebulizers (p < 0.001). The fine particle fraction (FPF), < 3 μm, of VixOne with holding chamber, was significantly higher (p < 0.001) and the mass median aerodynamic diameter (MMAD) was significantly lower (p = 0.022) than that with T-piece. The NebuTech and Kit had lower FPF and higher MMAD with holding chamber compared to T-piece (p < 0.05). There was no significant difference in the USAL24 and the emitted aerosol between the 3JNs with holding chamber or T-piece. Holding chamber did not significantly increase the emitted aerosol or USAL24 responsible for the side effect but improved the FPF < 3 μm and MMAD, responsible for lung deposition, with VixOne-JN only. Holding chamber, or similar add-on device, can be used with other nebulizers other than the VixOne, not to increase the inhaled dose but as a fugitive aerosol saver.

Evaluation of the Bioavailability and Pollution Indexes of Some Toxic Metals in Polluted Soils from an Abandoned Mining Area

The paper presents soil quality assessment using pollution and bioavailability indexes in order to highlight possible pollution generated by a decommissioned mining area in Certej, Deva County, Romania. Metals such as Cd, Cr, Cu, Ni, Pb and Zn were analyzed in pseudo-total and mobile form and the results were correlated with the content found in the vegetation collected from the same points during a previous study. The research shows a high mobility for Ni, Pb and Zn, respectively, a moderate mobility for Cd.

Chemical fractionation of heavy metals in fine particulate matter and their health risk assessment through inhalation exposure pathway.

Samples of PM2.5 were collected from an urban area close to a national highway in Agra, India and sequentially extracted into four different fractions: water soluble (F1), reducible (F2), oxidizable (F3) and residual fraction (F4) for chemical fractionation of arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), nickel (Ni) and lead (Pb). The metals were analyzed by inductively coupled plasma optical emission spectroscopy in each fraction. The average mass concentration of PM2.5 was 93 ± 24μgm-3.The total concentrations of Cr, Pb, Ni, Co, As and Cd in fine particle were 192 ± 54, 128 ± 25, 108 ± 34, 36 ± 6, 35 ± 5 and 8 ± 2ngm-3, respectively. Results indicated that Cd and Co had the most bioavailability indexes. Risk Assessment Code and contamination factors were calculated to assess the environmental risk. The present study evaluated the potential Pb hazard to young children using the Integrated Exposure Uptake Biokinetic Model. From the model, the probability density of PbB (blood lead level) revealed that at the prevailing atmospheric concentration, 0.302 children are expected to have PbB concentrations exceeding 10μg dL-1 and an estimated IQ (intelligence quotient) loss of 1.8 points. The predicted blood Pb levels belong to Group 3 (PbB < 5μg dL-1). Based on the bioavailable fractions, carcinogenic and non-carcinogenic risks via inhalation exposure were assessed for infants, toddlers, children, males and females. The hazard index for potential toxic metals was 2.50, which was higher than the safe limit (1). However, the combined carcinogenic risk for infants, toddlers, children, males and females was marginally higher than the precautionary criterion (10-6).

Isoniazid Pharmacokinetics in the Presence of Ofloxacin and Norfloxacin Antibiotics

The in vivo effects of norfloxacin (NXC) and ofloxacin (OXC) on isoniazid (INH) pharmacokinetics were investigated in 5 apparently healthy volunteers aged 18-39 years after an informed consent. The study was carried out in 3 phases with an interval drug wash out period of at least 1 week in between the phases. In phase 1 (INH alone), subject received 300 mg (usual adult dose) of INH. In phase 2 (INH + OXC), 300 mg of INH was coadministered with 200 mg of OXC, and in phase 3 (INH + NXC) each received 300 mg of INH together with 400 mg of NXC after 1-week drug wash period. Drugs were taken orally with 350 mL of water after an overnight fast, and the subject fasted 3 hours after drug. Plasma, saliva, and urine concentration of INH were predetermined at zero hour, then hourly until the eighth hour, 12 hours, 24 hours, and finally at 48 hours. The urine samples were further collected at 72 hours after drug(s) administration using validated methods. Various pharmacokinetics parameters were calculated. Various pharmacokinetic parameters of INH significantly differed when administered alone or in combination with OXC or with NXC. The mean saliva to plasma ratio of INH concentration was 0.14. The bioavailability indices of INH in the saliva and plasma were similar in all the groups. NXC and OXC reduced the extent and rate of absorption of INH. The determination of INH levels in saliva may be useful in therapeutic drug monitoring and pharmacokinetic studies.

Nitrate-responsive oral microbiome modulates nitric oxide homeostasis and blood pressure in humans

Imbalances in the oral microbial community have been associated with reduced cardiovascular and metabolic health. A possible mechanism linking the oral microbiota to health is the nitrate (NO3-)-nitrite (NO2-)-nitric oxide (NO) pathway, which relies on oral bacteria to reduce NO3- to NO2-. NO (generated from both NO2- and L-arginine) regulates vascular endothelial function and therefore blood pressure (BP). By sequencing bacterial 16S rRNA genes we examined the relationships between the oral microbiome and physiological indices of NO bioavailability and possible changes in these variables following 10 days of NO3- (12 mmol/d) and placebo supplementation in young (18–22 yrs) and old (70–79 yrs) normotensive humans (n = 18). NO3- supplementation altered the salivary microbiome compared to placebo by increasing the relative abundance of Proteobacteria (+225%) and decreasing the relative abundance of Bacteroidetes (−46%; P < 0.05). After NO3-supplementation the relative abundances of Rothia (+127%) and Neisseria (+351%) were greater, and Prevotella (−60%) and Veillonella (−65%) were lower than in the placebo condition (all P < 0.05). NO3- supplementation increased plasma concentration of NO2- and reduced systemic blood pressure in old (70–79 yrs), but not young (18–22 yrs), participants. High abundances of Rothia and Neisseria and low abundances of Prevotella and Veillonella were correlated with greater increases in plasma [NO2-] in response to NO3- supplementation. The current findings indicate that the oral microbiome is malleable to change with increased dietary intake of inorganic NO3-, and that diet-induced changes in the oral microbial community are related to indices of NO homeostasis and vascular health in vivo.

Evaluation of creatinine as a urine marker and factors affecting urinary excretion of magnesium by dairy cows

Nutrient balance studies require measuring urine volume, and urinary excretion can be used to assess Mg bioavailability. A less laborious method than total collection of urine could make balance studies more feasible and expand the utility of using urinary Mg as an index of bioavailability, but the method needs to be accurate and sensitive. Sampling interval can affect accuracy because excretion must be at steady state. Two experiments were conducted to (1) determine whether urinary creatinine could be used to accurately estimate urinary output of nutrients markedly excreted via urine (N, K, Na, S, and Mg; experiment 1) and (2) determine the appropriate sampling schedule to evaluate Mg excretion after abrupt diet changes (experiment 2). Experiment 1 was originally designed to evaluate the interaction of monensin [0 vs. 14 mg of monensin/kg of dry matter (DM)] and Mg source (MgO vs. MgSO4; total diet Mg: 0.36% of DM) under antagonism from increased dietary K (2.11% of DM) on urinary Mg excretion. Experiment 2 evaluated the interaction of Mg concentration (basal vs. supplemental MgO; total diet Mg: 0.20 vs. 0.42% of DM) and K (basal vs. supplemental K2CO3; total diet K: 1.60 vs. 2.57% of DM) on urinary Mg excretion over time. Using 4-d composite samples from total collection of urine (n = 34 cow-periods), the average daily excretion of creatinine was similar to previous estimates (29.0 ± 1.16 mg of creatinine/kg of body weight) but was variable among cows (root mean squared error = 2,980 mg/d; 14% of mean). Treatment-average estimated excretion of urine and urinary N, K, Na, S, and Mg were similar to actual values; however, differences between actual and estimated values could be substantial for individual cows. Using the mean creatinine excretion per kilogram of body weight for all cows to estimate urine eliminates the lack of fit variance resulting in artificially low within-treatment variation for estimated urine volume. The standard error of the mean for estimated urine volume was 23% less (1.93 vs. 2.51) than that for actual urine production. This inflated the type I error rate, and, consequently, statistical inferences on N and K excretion differed when urine output was estimated rather than measured. The standard error of the mean for excretion of Mg calculated with actual or estimated urine production were almost identical (0.92 vs. 0.97); however, similar standard error of the mean was likely caused by differences in the covariance of urinary Mg concentration with estimated or actual urine output. Based on spot sampling (experiment 2), urinary Mg reached steady state by 2 d following an increase in dietary K regardless of Mg level, whereas excretion of urinary Mg following an increase in dietary Mg continued to increase through 7 d. Estimating nutrient excretion with urinary creatinine and body weight on average is accurate, but variance is likely underestimated. Knowing the time course of urinary Mg excretion will improve the value of using urinary Mg concentration to assess diet adequacy or Mg bioavailability.

Mass distribution and health risk assessment of size segregated particulate in varied indoor microenvironments of Agra, India - A case study

Present study attempted to pave the way in study of indoor air pollution by Particulate Matter (PM) and picturesque a negative association of PM mass concentration levels with income (exposure determinant) at household level in Agra, India. Size resolved composition of PM (>2.5 μm, 2.5–1.0 μm, 1.0–0.5 μm and 0.5–0.25 μm) was sampled through a cascade impactor that examined mass distribution of 11 metals i.e. Fe, K, Mg, Ni, Mn, Pb, Zn, Ca, Cr, Cu and Al; subsequently determined with ICP-AES. Results revealed the prime association of Fe, Ca, K, Cr and Cu with coarse sized particulates while the remaining metals were associated with fine PM. Their source identification was confirmed through enrichment factor calculation and correlational analysis. Calculated bioavailability index revealed higher value for smaller size fraction (0.5–0.25 μm) inferring higher chances of getting adsorbed into the body. Assessed health hazard for individual metals identified greater risk posed to adults than children by different size fractionated particles. Moreover, the study made a newer attempt by elucidating the fact that people residing in low income households relying on solid fuels (and/or chulha) are subjected to higher cancerous (2.3–14.8 fold) and non-cancerous (1.5–2.3 fold) risk than those living in safer environment.

Effect of Feeding Tanniferous Oak Leaves on Nutrient Utilization, Serum Mineral Profile and Biochemical Indices in Goats

A 120 days growth study was conducted to assess the effect of tanniniferous oak leaves (Quercus semecarpifolia) on nutrient utilization, mineral bioavailability, and biochemical indices in goats. Eighteen growing kids (13.13 ± 0.99 kg; 7–9 months) were randomly divided into three homogenous groups of six each in a completely randomized design and fed native grass hay (Heteropogon contortus) in T1 (control), oak leaves (Quercus semecarpifolia) in T2 and supplemental tannic acid with grass hay in T3 keeping the concentrate mixture constant in all the treatments. At 90 days post feeding, a metabolism trial of six days duration was conducted. Blood was collected on day 0, 60 and 120. The nutrient intake per unit metabolic body size was higher (P < 0.05) in T2 than T1 and T3 without any alteration in plane of nutrition. Balance of Ca, Co, Cu, and Mn was higher (P < 0.05) in oak leaves fed goats, which was further reflected as higher (P < 0.05) serum mineral level of Ca and Mn in those animals. Serum urea level was lower (P < 0.05) in the oak leaves fed group (T2), whereas the serum cholesterol values were lower (P < 0.05) in T2 and T3. The levels of different serum enzymes viz. alkaline phosphatase and alkaline transaminase were higher (P < 0.05) in tannic acid supplemented group. These results suggest that feeding of oak leaves (condensed tannin, 0.85% and hydrolysable tannin, 4.4% in diet) improved bioavailability of Ca and Mn in goats as compared to animals fed local grass hay with or without supplementation of tannic acid.

Bioavailability of trace metals in sediments of a recovering freshwater coastal wetland in China's Yellow River Delta, and risk assessment for the macrobenthic community

We investigated the speciation of trace metals and their ecological risks to macrobenthic communities in a recovering coastal wetland of China's Yellow River Delta during the freshwater release project. We established 16 sampling sites in three restoration areas and one intertidal reference area, and collected sediments and macrobenthos four times from 2014 to 2015. The instability index for the trace metals showed a moderate risk for Mn and a high risk for Cd. For both Mn and Cd, the carbonate and FeMn-bound fractions appear to contribute mostly to the instability and bioavailability indexes, but for Cd, the exchangeable fraction also have a much higher contribution. The bioavailability index indicated higher bioavailability of trace metals in freshwater restoration areas than that in the intertidal area. The single-factor contamination index indicated that most trace metal concentrations in the macrobenthos were in excess of the national standard. The biota-sediment accumulation factor suggested that the macrobenthos accumulated most As, Cd, and Cu. Redundancy analysis showed clear relationships between the macrobenthos and sediment metal concentrations. Our results will help wetland managers to assess the bioaccumulation risks based on metal speciation, and to improve management of these recovering freshwater wetland ecosystems.

Metabolites of flavonoid compounds preserve indices of endothelial cell nitric oxide bioavailability under glucotoxic conditions

We hypothesized that metabolites of dietary flavonoids attenuate impairments in nitric oxide (NO) bioavailability evoked by glucotoxic conditions mimicking Type 1 or 2 diabetes. To test this, human aortic endothelial cells were treated with either vehicle control, quercetin-3-O-glucoronide, piceatannol or 3-(3-hydroxyphenyl)propionoic acid for 24 h. These are metabolites of quercetin, resveratrol and proanthocyanidin, respectively. Next, cells were exposed to control (5 mM) or high (25 mM) glucose conditions for 48 h, followed by insulin treatment (100 nM, 10 min) to stimulate NO production. In control glucose conditions NO production, phosphorylated to total endothelial nitric oxide synthase (p-eNOSser1177: eNOS), and phosphorylated to total Akt (p-AktSer473: Akt) were all increased by insulin stimulation. This response was abolished during high glucose conditions. Pretreatment of cells with flavonoid metabolites prior to high glucose challenge preserved insulin stimulated increases in NO production, p-AktSer473: Akt and p-eNOSSer1177: eNOS. These effects may be secondary to oxidative stress as pretreatment with all flavonoid metabolites prevented elevations in reactive oxygen and nitrogen species in response to high glucose. These data support the hypothesis that beneficial effects of flavonoids on endothelial cell function in the context of glucotoxicity, at least in part, are secondary to their metabolites.

Chemical Speciation and Health Risk Assessment of Fine Particulate Bound Trace Metals Emitted from Ota Industrial Estate, Nigeria

In this study carcinogenic and non-carcinogenic health risk due to exposure to PM2.5-bound trace metals from an industrial area in Southwestern Nigeria was estimated. A four-step chemical sequential extraction procedure was employed for the chemical extraction of arsenic (As), cadmium (Cd), chromium (Cr) copper (Cu), manganese (Mn), nickel (Ni), and zinc (Zn). Samples were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). Results reveal Cr and Cu as the most dominant exchangeable fraction metals, indicating possibility of their being readily soluble once PM2.5 is inhaled. Cd and Cr record the highest bioavailability index of 0.7. The cumulative lifetime cancer risks due to inhalation exposure for adults (4.25×10-2), children 1-6 years old (4.87×10-3), and children 6-18 years old (1.46×10-2) were found above Environmental Protection Agency’s acceptable range of 1×10-6 to 1×10-4. The hazard index values for all studied trace metals suggest significant potential for non-carcinogenic health risks to adults and children. The choice of chemical speciation as an essential tool in facilitating a better predictive insight on metal bioavailability and toxicity for immediate remediation action has been highlighted.

140 - EPR spectroscopy quantification of HbNO as an index of vascular nitric oxide bioavailability in vivo

140 - EPR spectroscopy quantification of HbNO as an index of vascular nitric oxide bioavailability in vivo

Impact of highway traffic and the acoustic screen on the content and spatial distribution of heavy metals in soils

Recent years have witnessed intensification of road traffic and, with it, the amount of substances emitted by vehicles. Such emissions need to be monitored for public health purposes. The aim of this study was to evaluate the impact of the highway traffic on the total content and bioavailability of Zn, Cu, Ni, Cd, Cr and Pb in nearby soils as well as influence of an acoustic screen on spatial distribution of the metals. The material included 40 soil samples collected from 15 research points located 5, 10, 25 and 50 m away from the road acoustic screen and from 4 points between the screen and the highway. Additionally, 5 research points were located next to the metal barrier. Selected physicochemical properties of soils were determined: soil texture, soil pH, TOC and CaCO3 content. The total content of heavy metals in the soils was determined by AAS after digestion in aqua regia and bioavailable forms in 1 M diethylenetriaminepentaacetic acid. The research found low impact of the highway traffic on the content of heavy metals in soils; however, due to a very short period of this potential impact (5 years), the moderately polluted category of geo-accumulation index of cadmium and high bioavailability of lead indicate the need of repeating the research within the next several years. Furthermore, the road acoustic screen significantly influenced spatial distribution of the metals in soils.

Speciation and mobility of lead in shooting range soils

The mobility and bioavailability of lead (Pb) in seven military shooting range soils found in eastern and north eastern Botswana were studied using sequential extraction procedure. The different forms of Pb and their reactivity in the soil help explain their speciation, mobility and bioavailability in the environment. Mobility of Pb in the berm soils in all the seven shooting ranges was found to be over 90% implying high Pb lability. The bioavailability index of Pb was in the range 60–90%, an indication that most of the Pb can be available for plant uptake. Sequential extraction studies indicate that the partitioning of Pb was mostly confined to the carbonate compartment in all the shooting ranges. All the seven shooting ranges failed the Synthetic Precipitation Leaching Procedure (SPLP) with SPLP Pb concentrations exceeding United States Environmental Protection Agency (USEPA) 0.015 mg/kg critical level of hazardous waste, posing a pollution threat to surface and groundwater.

Exposure assessment of children to particulate matter and gaseous species in school environments of Pune, India

Indoor air quality of schools is a subject of great significance for the assessment of the effects of children exposure to air pollution. In order to characterize the indoor air quality, coarse and fine particulate matter (PM) levels, concentration of gaseous pollutants (CO2, SO2, NO2, O3) and major anions, elemental concentration, morphology and risk assessment were evaluated from the samples collected in different naturally ventilated schools in Pune, India. Mass concentration of both coarse and fine PM exceeded 5 times WHO standards, which clearly indicates the insufficient fresh air in school buildings of Pune in terms of PM. The average concentration of gaseous pollutants were within prescribed limits of NAAQS except CO2 which was higher in concentration than the limit set for confined spaces, thus showing the inadequate air exchange rates in the studied schools. The Ca showed significant dominance among the analyzed metals in both fraction of PM followed by Mg, Na and K. Cd showed higher bioavailability index among the carcinogenic metals leading to health hazards to exposed children. The cancer risk for Cr, Cd, Ni, and Pb in both sized PM were much higher than the acceptable limits of USEPA. Average anionic concentration followed the similar pattern for both sized fraction of PM and the trend was NO3− > SO42− > Cl− > F−. The morphological analysis revealed the presence of various shaped particles composed of various constituents of Si, C and Ca. Questionnaire survey and personnel interview showed the prevalence of cold, running nose, cough, fever and eye irritation among the studied school children exposed to the PM and gaseous species. The health problems such as cold, cough and fever were found to be the main cause of absenteeism of children.

Distribution of remaining Cd in MSWI fly ash washed with nitric acid

Municipal solid waste incineration (MSWI) fly ash is by-product and hazardous waste produced from MSWI plant. In the MSWI fly ash there are high contents heavy metals, among which cadmium (Cd) is more active and toxic. Although inorganic acid leaching is an effective way to remove heavy metals out from the MSWI fly ash and nitric acid has great efficiency for Cd removal, little literature reported the redistribution of remaining Cd in the MSWI fly ash. This investigation focused on the change of different factions (exchangeable, bound to carbonates, bound to Fe–Mn oxides, bound to organic matter and residual) of Cd in treated (i.e. washed with nitric acid) MSWI fly ash. Sequence extraction procedures (SEP) have been used to derive different fractions of Cd, results indicated that fractions of Cd have changed significantly after nitric acid washing procedures. Due to the changes of main compounds and microstructures stable Cd (bound to organic matter and residual) had opportunity to leach out, which resulted in a higher potential risk (or higher bioavailability index) for living creatures, although the total amount of Cd decreased. X-ray diffraction (XRD) and images of scanning electron microscope (SEM) proved these changes in washed MSWI fly ash.

Contamination and comprehensive risk assessment of heavy metals in Liangtan River, Chongqing, China

Distribution and fraction of heavy metals (Pb, Cr, Zn, and Mn) in water and sediment in Liangtan River, Chongqing was analyzed using the atomic absorption spectrometry method. Pearson correlation coefficient, bioavailability index, geoaccumulation index and potential ecological risk index were introduced to classify the source and assess the environmental risk of the heavy metal. Pb, Cr, and Zn mainly existed in residual fraction and fraction bounded to Fe–Mn oxides while Mn mainly existed in the fraction bounded to carbonates and the residual fraction. Mn and Pb, Zn and Cr in the sediment were confirmed originating from, separate common sources. Igeo and were both in the order of Pb > Zn > Cr > Mn. Geoaccumulation indexes demonstrated that the Liangtan River has been heavily polluted by Pb and Zn with the class of 2–4 and 2–3, independently. From viewpoint of the whole Liangtan River, the mean RI (45.1) belonged to low risk level.

Using morphological structure of Penicillium funiculosum as a bioavailability index during the biodegradation of PHB, PCL and their blends

Using morphological structure of Penicillium funiculosum as a bioavailability index during the biodegradation of PHB, PCL and their blends

Seasonal Quality Assessment of Agricultural Soils along the Bank of Tungan Kawo Dam, Kontagora, Nigeria

This research work studies the impacts of irrigation and other agricultural practices on the soil along the bank of Tungan Kawo dam. The experimental analysis evaluates the soil physicochemical parameters and metal (Cd, Cu, Cr, Ni, Fe, Mn, Pb and Zn) concentrations using sequential extractions. The physicochemical parameters of the soils across the sites indicated values reported for less polluted soils. Also, analysis of total metals in the soils indicated lower concentration of all metals evaluated than recommended standard limits with exception of Cd. The results of sequen tial extraction of heavy metal in soil sample indicated that all metals were mainly associated with the residual, Fe-MnO and organic bound fractions. The residual fraction has the maximum concentration of metals especially in cool and dry season for Cr, Cu, Ni, Pb and Zn, whereas only a small fraction of all the heavy metal is extracted in water soluble, exchangeable and carbonate bound fractions. It indicates that the bioavailability index is low. Hence, mobility of the heavy metals by the surrounding plants grown on the soils is low.

Abstract 12275: Knock-down of Insulin-like Growth Factor-1 Receptor in the Endothelium Decreases Anti-oxidant Capacity of Aorta, Leading to Increased Atherosclerosis

Systemic infusion of insulin-like growth factor-1 (IGF-1) in Apoe-deficient mice exerts anti-atherogenic effects by reducing oxidative stress and pro-inflammatory responses in lesions, yet precise mechanisms remain elusive. We have shown that smooth muscle specific IGF-1 overexpression does not reduce atherosclerotic burden, suggesting that smooth muscle cells do not mediate anti-atherogenic effects of IGF-1. The endothelium is integral in atherogenesis, however a potential role of endothelial IGF-1 receptor (IGF1R) signaling in atherogenesis is unknown. To investigate, we generated Apoe-deficient/endothelial IGF1R-knockdown (En-IGF1R-KD) mice, which are Igf1r-floxed and express Cre recombinase driven by the Cdh5-promoter. IGF1R expression levels were lower by 60% in endothelial cells isolated from En-IGF1R-KD mice compared to IGF1R-flox cells. After 12 weeks of high-fat diet feeding, En-IGF1R-KD mice had more atherosclerotic plaque than IGF1R-flox control (Oil Red O staining of en face aorta, 33±8% increase, P&lt;0.05), indicating that loss of endothelial IGF1R signaling enhanced atherogenesis. Intriguingly, En-IGF1R-KD did not alter systolic blood pressure (IGF1R-flox; 119.5±2.6 vs. En-IGF1R-KD; 119.1±2.0 mmHg) or plasma nitrate/nitrite levels (index of nitric oxide bioavailability, IGF1R-flox; 8.6±0.4 vs. En-IGF1R-KD; 7.3±0.9 uM). Vasorelaxation to acetylcholine (Ach) was equivalent in aortas of En-IGF1R-KD and IGF1R-flox mice after high-fat diet feeding, suggesting that endothelial function was not affected by En-IGF1R-KD. Intriguingly, high-fat diet feeding made aortas hyporesponsive to Ach both in En-IGF1R-KD and IGF1R-flox mice, and in normal chow fed mice En-IGF1R-KD aortas were more responsive to Ach than IGF1R-flox aortas, indicating that loss of IGF-1 signaling improved endothelial function. On the other hand, anti-oxidant capacity as measured by Hydroxyl Radical Antioxidant Capacity Activity Assay was significantly lower in En-IGF1R-KD aorta by 30.0±6.7%, consistent with anti-oxidant effects of IGF-1 on endothelial cells. In summary, our results indicate that IGF1R signaling in the endothelium is atheroprotective, and that this atheroprotective effect is mediated via an anti-oxidant mechanism.