Antarctic Krill Oil Research Articles

Antarctic Krill Oil Attenuates Oxidative Stress via the KEAP1-NRF2 Signaling in Patients with Coronary Heart Disease.

Background Antarctic krill oil (AKO) has strong antioxidant activities and is effective for alleviating coronary heart disease (CHD). Kelch-like ECH-associated protein 1-NF-E2-related factor 2 (KEAP1-NRF2) axis is a crucial antioxidant signaling pathway. Thus, AKO may exert its antioxidant effects on CHD patients via KEAP1-NRF2 signaling. Methods AKO fatty acid (FA) profiles were analyzed by using gas chromatography (GC). One hundred CHD patients were divided into the intervention (IG, AKO) and control (CG, placebo) groups. Before and after 1, 2, and 3 months of intervention, we measured serum levels of reactive oxygen species (ROS), 8-hydroxy-2-deoxyguanosine (8-OHdG), nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH), and glutathione peroxidase (GPx), and KEAP1 and NRF2 levels in peripheral blood leukocytes (PBLs). Serum FAs were measured by GC at baseline and after 3-month intervention. Results AKO contains rich eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which is more than 27% of total FA. The levels of EPA and DHA, KEAP1, and NRF2 in the IG group were higher than those in the CG group (p < 0.05). Serum levels of ROS, 8-OHdG, NO, and MDA in the IG group were lower than those in the CG group, whereas the levels of SOD, GSH, and GPx in the IG group were higher than those in the CG group (p < 0.05). Serum levels of saturated fatty acids (UFA) in the IG group were higher than those in the CG group, whereas reverse results were obtained for the levels of saturated fatty acids (SFA). Serum levels of EPA and DHA had a strong negative relationship with the level of ROS, whereas the ROS level had a strong negative relationship with the levels of KEAP1-NRF2. Conclusion AKO increases antioxidant capacities of CHD patients via the KEAP1-NRF2 signaling in the PBL.

Effects of different proteases enzymatic extraction on the lipid yield and quality of Antarctic krill oil.

This study was investigated the effects of six proteases (papain, compound proteinase, acidic protease, neutrase, pancreatin, and alcalase) on the lipid yield and quality of krill oil. The result shown that the krill oil extracted by alcalase and compound proteinase led to comparatively higher lipid yields (5.29% and 4.90%, respectively), Content of tocopherols and vitamin A, the content of omega‐3 polyunsaturated fatty acids (PUFAs) and phospholipids extracted by alcalase was relatively higher. Control and alcalase had comparatively higher concentration of astaxanthin. On the whole, compared with the extraction of solvent, enzymatic hydrolysis could improve the quality and the lipid yield of krill oil. Therefore, enzymatic hydrolysis could be used as a better method to extract krill oil.

Effect of Antarctic Krill Oil on Astaxanthin in Rat Serum

Effect of Antarctic Krill Oil on Astaxanthin in Rat Serum

Development of a 450 nm Laser Irradiation Desorption Method for Fast Headspace Solid‐Phase Microextraction of Volatiles from Krill Oil (Euphausia superba)

A laser irradiation desorption (LID) method is developed using a 450 nm blue semiconductor laser and gas chromatography mass spectrometry (GC/MS) for analyzing the flavor of Antarctic krill oil (Euphausia superba). The experimental parameters of LID are optimized by response surface methodology (RSM), and the optima are obtained as follows; laser power (10 W), irradiation time (5 min), and sample volume (3 g). The results show that a total of 41 volatile molecular species are detected, including six alcohols, 10 aldehydes, five ketones, 14 hydrocarbons, and six other compounds. Compared with the conventional heating assisted desorption technique, the LID can release volatile molecular species with higher abundance in a considerably reduced extraction time from 30 to 5 min. Finally, the proposed method is validated in terms of sensitivity, precision, linearity, and recovery, which demonstrate its advantages of high efficiency and simplified procedure.Practical Applications: An LID method is developed using a 450 nm blue semiconductor laser for analyzing the flavor of Antarctic krill oil (E. superba). Compared with the conventional heating assisted desorption technique, the LID can release more volatile molecular species with higher abundance in a considerably shorter extraction time, and the intensive laser power does not induce the autoxidation of polyunsaturated fatty acids. It shows the advantages of a highly efficient, and simplified procedure.A laser irradiation desorption (LID) method is developed using a 450 nm blue semiconductor laser for analyzing the flavor of Antarctic krill oil (Euphausia superba).

Antarctic Krill (Euphausia superba) Oil: A Comprehensive Review of Chemical Composition, Extraction Technologies, Health Benefits, and Current Applications.

Antarctic krill (Euphausia superba) oil has been receiving increasing attention due to its nutritional and functional potentials. However, its application as a novel food ingredient has not yet been fully explored. This review summarizes the chemical composition, extraction technologies, potential health benefits, and current applications of krill oil, with the aim of providing suggestions for its exploitation. Krill oil is a unique lipid consisting of diverse lipid classes and is characterized by a high concentration (39.29% to 80.69%) of phospholipids (PLs) associated with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). It also contains considerable amounts of bioactive minor components such as astaxanthin, sterols, tocopherols, vitamin A, flavonoids, and minerals. The current technologies used in krill oil production are solvent extraction, nonsolvent extraction, super/subcritical fluid extraction, and enzyme-assisted pretreatment extraction, which all greatly influence the yield and quality of the end-product. In addition, krill oil has been documented to have various health benefits, including anti-inflammatory effects, cardiovascular disease (CVD) prevention, women's health, neuroprotection, and anticancer activities. Although krill oil products used for dietary supplements have been commercially available, few studies have attempted to explore the underlying molecular mechanisms to elucidate how exactly the krill oil exerts different biological activities. Further studies should focus on this to improve the development of krill oil products for human consumption.

Antarctic krill oil promotes longitudinal bone growth in adolescent male mice

The effects of dietary supplementation with Antarctic krill oil (AKO) on longitudinal bone growth in adolescent male Institute for Cancer Research (ICR) mice for 21 days were investigated. Histological results showed that AKO promoted longitudinal bone growth, increased skeletal mineral content and strength, enhanced entochondrostosis supported by higher longitudinal bone growth rate and growth plate height. Then, the potential mechanisms responsible for these observations were measured, results showed that AKO increased the secretion of the GH-IGF-1 pathway and entochondrostosis-related factors in serum increased the expression of IGF-1 in the liver and bone, which promoted proliferation and differentiation of chondrocytes, vascular invasion and bone formation related gene expression. AKO promoted longitudinal bone growth, using the GH-IGF-1 pathway, suggesting that AKO might be a potential functional food to improve growth potential of adolescents.

Effect of Antarctic Krill Oil on Astaxanthin in Rat Serum

To explore whether the antarctic krill oil has an impact on astaxanthin ester absorption process, provide scientific basis and theoretical support for the development and application of Antarctic krill oil in functional food or special medical food. Methods: 150 Wistar male rats were randomly divided into 5 groups: blank control group, 0.208g oil/kg.bw Antarctic krill oil group, 1.25mg/kg body wt of astaxanthin group, 1.25mg/kg body wt of astaxanthin+0.208g oil/kg.bw Antarctic krill oil group and 1.25mg/kg body wt of astaxanthin+0.208g oil/kg.bw Fish oil group.Samples were collected at ten time points(0, 0.5,1,2,4,8,10,12,16,24h) after administering a single oral dose corresponding to rats via the intragastric gavage mode and the astaxanthin concentrations in samples were detected using Hplc.Results: The maximum concentration of astaxanthin in the serum of ASTA- krill oil group was delayed by 6 h compared with the ASTA group. The highest concentration of ASTA- krill oil group in serum was was 5.3 times of ASTA- Fish oil group, which was 8.4 times that of ASTA group. The serum AUC values of ASTA-krill oil group,the ASTA group and the ASTA-Fish oil group were 108.39±2.34ug∙h/L, 14.35±0.21 ug∙h/L, 23.39±0.46 ug∙h/L, respectively., reflecting that the bioavailability of ASTA- krill oil in rats is higher than that of ASTA group, which is better than ASTA- Fish oil .Conclusion: The serum absorption rate of the ASTA- krill oil group are excellent. Antarctic krill oil promotes the bioavailability of astaxanthin and provides scientific basis and theoretical support for the development and application of functional foods or special medical foods.

Oil from Antarctic krill (Euphausia superba) facilitates bone formation in dexamethasone-treated mice.

Glucocorticoids are the leading cause of secondary osteoporosis. In the current study, the in vivo effects of Antarctic krill (Euphausia superba) oil (AKO) on dexamethasone-treated mice were investigated. Results showed that AKO significantly prevents bone loss, as evidenced by improved bone mineral density, biomechanical strength, and cancellous bone microstructure. Fluorescence double-labeling of femur showed that AKO induces new bone formation. Toluidine blue staining of marrow cavity indicated that AKO increases the number of trabecula, and decreases the generation of adipose cells. Runt-related transcription factor 2 (Runx2) and Peroxisome proliferator-activated receptor γ (PPARγ) are the switches for osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells, respectively. AKO significantly promoted the expression of Runx2 protein, and reduced PPARγ expression in bone tissue. Furthermore, AKO increased the mRNA expression of osteogenesis-related genes and decreased the expression of adipogenesis-related genes. In conclusion, AKO improved glucocorticoid-induced osteoporosis via promoting bone formation.

Antarctic Krill Oil improves articular cartilage degeneration via activating chondrocyte autophagy and inhibiting apoptosis in osteoarthritis mice

In this study, the in vivo effects of Antarctic krill oil (AKO) on cartilage degeneration in destabilization of the medial meniscus (DMM) mouse were investigated. Results showed that AKO improved the cartilage structure, inhibited chondrocyte hypertrophic differentiation and inhibited abnormal apoptosis in articular cartilage. Autophagy is a self-protective metabolic process required for maintaining cartilage homeostasis. We observed that expression of mTOR were reduced, which was consist with high PPAR-γ levels. The expression of key genes related to autophagy, including LC-3B, Beclin-1, ATG-5, and BNIP-3 were significantly enhanced after treatment with AKO. In addition, we observed that AKO suppressed the expression of key genes in p53-dependent mitochondrial apoptotic pathway, such as p53, Bax, Bid, cytochrome c, caspase-9, caspase-3 and enhanced the expression of anti-apoptotic genes, including Bcl-2 and Bcl-xl. These findings provided a new perspective for the effect of AKO on OA, which associated with the regulation of autophagy and apoptosis.

The Protective Effect of Antarctic Krill Oil on Cognitive Function by Inhibiting Oxidative Stress in the Brain of Senescence-Accelerated Prone Mouse Strain 8 (SAMP8) Mice.

The results of Morris water maze, Barnes maze test and open-field test indicated that Antarctic krill oil (AKO) improved the cognitive function and anxiety of SAMP8 mice. AKO reduced the Aβ42 level in hippocampus of SAMP8 mice. AKO ameliorated oxidative stress in brain rather than in serum and liver of SAMP8 mice.

An Effective Extract Method of Phospholipids from Antarctic Krill &amp;lt;em&amp;gt;Euphausea superba&amp;lt;/em&amp;gt;

Phospholipids are one of the major bioactive ingredients of Antarctic krill Euphausea superba. A feasible and effective extraction method of Antarctic krill oil was investigated and modified by orthogonal test which the ratio of solid to liquid was 1:2.5, extraction time was 5 min, ratio of ethyl acetate (EA) and n-butanol (BuOH) was 1:1. With this method, the extract of krill oil has a higher phospholipids content of 27.7% - 42.3%, together with total oil yields of 4.15% - 6.18%.

Antarctic Krill Oil Diet Protects against Lipopolysaccharide-Induced Oxidative Stress, Neuroinflammation and Cognitive Impairment.

Oxidative stress and neuroinflammation are implicated in the development and pathogenesis of Alzheimer’s disease (AD). Here, we investigated the anti-inflammatory and antioxidative effects of krill oil. Oil from Euphausia superba (Antarctic krill), an Antarctic marine species, is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We examined whether krill oil diet (80 mg/kg/day for one month) prevents amyloidogenesis and cognitive impairment induced by intraperitoneal lipopolysaccharide (LPS) (250 µg/kg, seven times daily) injections in AD mice model and found that krill oil treatment inhibited the LPS-induced memory loss. We also found that krill oil treatment inhibited the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and decreased reactive oxygen species (ROS) and malondialdehyde levels. Krill oil also suppresses IκB degradation as well as p50 and p65 translocation into the nuclei of LPS-injected mice brain cells. In association with the inhibitory effect on neuroinflammation and oxidative stress, krill oil suppressed amyloid beta (1–42) peptide generation by the down-regulating APP and BACE1 expression in vivo. We found that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (50 and 100 µM) dose-dependently decreased LPS-induced nitric oxide and ROS generation, and COX-2 and iNOS expression as well as nuclear factor-κB activity in cultured microglial BV-2 cells. These results suggest that krill oil ameliorated impairment via anti-inflammatory, antioxidative, and anti-amyloidogenic mechanisms.

Effects of Antarctic krill oil on lipid and glucose metabolism in C57BL/6J mice fed with high fat diet

BackgroundObesity and other metabolic diseases have become epidemic which greatly affect human health. Diets with healthy nutrition are efficient means to prevent this epidemic occurrence. Novel food resources and process technology were needed for these purpose. In this study, Antarctic krill oil (KO) extracted from a dry krill by a procedure of hot pump dehydration in combined with freezing-drying was used to investigate health effect in animals including the growth, lipid and glucose metabolism.MethodsC57BL/6J mice were fed with a lard based high fat (HF) diet and substituted with KO for a period of 12 weeks in comparison with low fat normal control (NC) diet. Mice body weight and food consumption were recorded. Serum lipid metabolism - of C57BL/6J mice serum was measured. A glucose tolerance tests (GTTs) and pathology analysis of mice were performed at the end of the experiment.ResultsThe KO fed mice had less body weight gain, less fat accumulation in tissue such as adipose and liver. Dyslipidemia induced by high fat diet was partially improved by KO feeding with significant reduction of serum low density lipoprotein-cholesterol (LDL-C) content. Furthermore, KO feeding also improved glucose metabolism in C57BL/6J mice including a glucose tolerance of about 22% vs. 32% of AUC (area under the curve) for KO vs HF diet and the fast blood glucose level of 8.5 mmol/L, 9.8 mmol/L and 9.3 mmol/L for NC, HF and KO diet groups, respectively. In addition, KO feeding also reduced oxidative damage in liver with a decrease of malondialdehyde (MDA) content and increase of superoxide dismutase (SOD) content.ConclusionThis study provided evidence of the beneficial effects of KO on animal health from the processed technology, particularly on lipid and glucose metabolism. This study confirmed that as the Antarctic krill was extracted with a procedure of efficient energy, it might make it possible for Krill oil to be available for food industry.

Utilization of waste protein from Antarctic krill oil production and natural dye to impart durable UV-properties to cotton textiles

Cleaner production in the textile industry may be realized by replacing certain synthetic substances with natural materials, especially those that are industrial by-products, which offer the added benefit of increasing the value of the textiles. Since natural materials generally pose a low risk to both the human health and the environment owing to their biodegradability, the wastewater released from their manufacturing processes is less polluting, and therefore, it requires less resources and energy for treatment compared to wastewater loaded with synthetic substances. Herein, we report the use of a protein by-product recovered from the oil extraction process of Antarctic krill (Euphausia superba) to replace traditional mordanting agents in the dyeing of cotton with tannin-rich natural dye extracted from the bark of Xylocarpus granatum. Antarctic krill protein pretreatment successfully improved the dyeability of the fabrics through the formation of insoluble complexes between the protein and tannin. The color parameters of the dyed samples were measured based on the CIE L*a*b* system. The obtained reddish-brown fabrics exhibited mostly good to excellent color fastness ratings in response to washing and other wet treatments. They also displayed durable UV protection properties, with the UPF rating reaching the maximum (50+) level, despite being washed for 50 cycles. Both the Antarctic krill protein and tannin contributed to improved UV protection efficiency due to the presence of UV-absorbing moieties and slight changes in the resulting fabric thickness and cover factor.

The Forms of Fluoride in Antarctic Krill (Euphausia superba) Oil Extracted with Hexane and its Removal with Different Absorbents

ABSTRACTKrill oils (KOs) were prepared using different extraction methods (hexane and supercritical carbon dioxide), different materials (heat-dried krill powder, freeze-dried krill powder, and freeze-dried krill tail meat powder), and different standing times during hexane extraction. The fluoride concentrations in the KOs were positively correlated with the protein concentrations. Absorbents were employed to remove fluoride from KO. Activated clay achieved the highest fluoride removal rate (70.66%), followed by calcium oxide (14.49%), activated carbon (11.97%), calcium chloride (9.32%), activated alumina (0.94%), and chitosan (0.52%). Meanwhile, the protein removal rates of the above absorbents were positively correlated with the fluoride removal rates.

E-configuration structures of EPA and DHA derived from Euphausia superba and their significant inhibitive effects on growth of human cancer cell lines in vitro

Many bioactive components such as poly-unsaturated fatty acids (e.g. EPA and DHA), phospholipids and astaxanthin are known in Antarctic krill (Euphausia superba) oil. The krill DHA and EPA are generally considered to be similar to natural ones. However, two chemical compounds which were separated from Antarctic krill oil and identified as EPA and DHA by HRESIMS and NMR acted much more effective inhibitive activities on growth of several cell lines (U937, K562, SMMC-7721, PC-3, MDA-MB-231, HL60 and MCF-7) than those from sturgeon liver and commercial fish oil. Taking MCF-7 as an example, the IC50 values of Antarctic krill EPA and DHA were 14.01 and 19.94μM，while the IC50 values of sturgeon liver and commercial fish EPA and DHA were 81.45, 73.13, 82.11 and 75.31μM, respectively. Raman spectra revealed that the Antarctic krill EPA and DHA have E-configuration structures, which were different from those in commercial fish oil. Additionally, the Antarctic krill EPA and DHA had no effects on human normal liver cell line HL7702. These results indicated that the Antarctic krill E-EPA and E-DHA had a great prospect in cancer therapy.

Oxidative stability and non‐enzymatic browning reactions in Antarctic krill oil (Euphausia superba)

SummaryAntarctic krill oil has gained much consideration recently due to its rich content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the form of phospholipids and its powerful antioxidant known as astaxanthin. To secure these valuable bioactive nutrients in krill oil, a gentle and immediate on‐board processing of freshly captured krill is recommended. Compared to fish oil, krill oil has a more complex matrix, which leads to the formation of additional compounds from non‐enzymatic browning reactions. Lipid oxidation occurs through different pathways in krill oil and cannot be detected through classical analytical techniques such as determination of peroxide and anisidine value. Therefore selection of appropriate methods to evaluate the oxidative stability of krill oil is of high importance.Development of lipid derived volatiles: (a &amp; b) 1‐penten‐3‐ol and (c &amp; d) 2‐pentylfuran in krill oil upon storage at two different incubation temperatures (20 and 40°C). The same pattern as (a &amp; b) was obtained for (Z)‐2‐penten‐1‐ol and benzaldehyde, whereas the same pattern as (c &amp; d) was obtained for 2‐heptanone and 2‐octanone. Values are mean ± SD (n = 3). Means sharing the same letter are not significantly different at 5% significant level. Reproduced from Lu et al. with permission from Elsevier.magnified image

Separation and characterization of acetone-soluble phosphatidylcholine from Antarctic krill (Euphausia superba) oil

Antarctic krill is the biggest fishery resource in the world with high content of phosphatidylcholine (PC) as a valuable natural product. A new method was developed to extract and separate Antarctic krill PC. The PC was extracted only by acetone from Antarctic krill oil and separated by silica gel column chromatography mixtures of chloroform and methanol as eluting solvents. Thin-layer chromatography, high-performance liquid chromatography, and Fourier-transform infrared spectroscopy analyses were used to characterize the acetone-soluble Antarctic krill PC. The purity of the purified PC was able to reach 97.77 ± 0.65 %, which provided a reference basis for the preparation of standard Antarctic krill PC. Moreover, it was found in the fatty acid analysis that the purified PC contained mainly five fatty acids, including palmitic acid (41.25 %), oleic acid (8.62 %), 7-hexadecenoic acid (4.60 %), EPA (31.34 %), and DHA (14.52 %). The result is helpful for the analysis of Antarctic krill PC’s molecular structures and the evaluation of its nutritional value.

High-performance thin layer chromatography determination of astaxanthin in Euphausia superba oil

The Antarctic krill (Euphausia superba) is a kind of marine zooplankton belonging among Crustacea [1]. It is the principal prey of many marine predators by reason of its gigantic population [2]. The study of Antarctic krill has become a hot research field in the past few decades. It is not only the key organism in the southern ocean but also the biggest fishery resource in the world. With its high content of astaxanthin as a valuable natural product [2, 3], it urgently awaits development and utilization. The ketocarotenoid astaxanthin (3,3 -dihydroxy, -carotene-4,4 -dione) and astaxanthin esters are the principal components of Antarctic krill pigment [4], and astaxanthin is one of most important carotenoids by virtue of its biologic functions as a vitamin A precursor and as a much more efficient antioxidant than -carotene and vitamin E [5]. It is also a natural coloring (in fish muscles, bird feathers, yolks, etc.), supports the immune system, has an anti-tumor effect, and protects from ultraviolet radiation [6–8]. Overall, astaxanthin can play an important role in healthcare and cosmetic manufacture, with enormous commercial and industrial prospects. As a general rule, high-performance liquid chromatography (HPLC) is preferred in astaxanthin assay due to its wide use all around the world [9], whereas the HPTLC technique with high sensitivity and resolution can also function excellently in the separation and purification of bioactive compounds from natural materials. In short, we aim to establish and validate an HPTLC method that is adapted to astaxanthin determination in Antarctic krill oil and that can be applied to other materials that contain astaxanthin. The astaxanthin in Antarctic krill is mostly in the form of astaxanthin esters for its molecular stabilization [10]. Some are diesters and others are monoesters, attributed to the two hydroxyls that can combine with different fatty acids at both ends of the astaxanthin molecule [11]. While the concentration of free astaxanthin was amall, all of it and other impurities are fat soluble and can be dissolved in low-polarity reagents; thus, n-hexane–acetone (7:2, v/v) was chosen to be the mobile phase after repeated attempts, combined with the high-performance silica gel 60 F254, which can accomplish the HPTLC separation within 10 min. The Rf value of the free astaxanthin was 0.32. It was necessary to apply the saponification procedure to release the astaxanthin combined with fatty acids because the concentration of free astaxanthin was from 5 1.0% to 85 5.0%, so that the qualification and quantification of astaxanthin can be carried out more successfully, as well as the further purification, since there was no standard for astaxanthin esters. KOH was essential in saponification, but it can result in significant degradation of astaxanthin, especially when the reaction temperature was high. There was almost no degradation of astaxanthin at 4 C [12]; therefore it was selected as the saponification temperature, and the maximum concentration of free astaxanthin can reach 89.7466%. The linear regression equation of astaxanthin after saponification is Y = 1309.2935 + 47.9693X (where Y is the response and X is the mass of astaxanthin). The correlation coefficient was found to be 0.9990, the RSD (relative standard deviation) was 2.56%, and the astaxanthin in the saponification sample was 0.7045 mg·mL–1; more data are shown in Table 1. The three main components in the original sample were separated without interference from other impurities, and the spectral evaluation of the samples showed the same maximum absorption ( max 476 nm) as the standard; therefore, the specificity of this method is verified. The RSD of intraday precision was 1.68% and the value of the interday precision was 5.07%. Both values were determined when the plates were stored in the dark. The accuracy was clarified as percent recovery, and the average recovery of astaxanthin was 98.53%.

Endothelial Mechanisms of Flow-Mediated Athero-Protection and Susceptibility

See related article, pages 97–105 The arterial endothelium survives remarkably well as the interface between blood and vessel wall in an environment of constantly changing biomechanical stresses as well as acute and chronic exposure to inflammatory stimulants (eg, cytokines and hypercholesterolemia respectively).1 Cell turnover, which tends to occur in regional clusters,2 is otherwise very low in this monolayer. The endothelium also plays an important regulatory role in the pathogenesis of vascular disease. The cells readily respond to diverse stimuli through a repertoire of mechanisms to enhance their own survival even as they facilitate inflammatory, proatherogenic responses in the subendothelial tissue. The necessity to be a responsive cellular interface probably accounts for much of the endothelial phenotype heterogeneity that exists between vascular beds as well as within discrete regions of the arterial circulation.3,4 Hemodynamic characteristics that vary with blood vessel geometry predict the location of arterial sites that are susceptible to atherosclerosis.5 Curved and branching vessel geometries create sites of flow separation that contain transient flow reversals, lower average shear stresses, and occasional turbulence, (collectively, disturbed flow) and that are predictive of lesion formation. In contrast, pulsatile unidirectional laminar flow (and higher average shear stresses) is associated with regions where atherosclerosis rarely occurs, despite there being equivalent exposure to plasma risk factors such as hypercholesterolemia throughout the circulation. Although the signatures of endothelial phenotype in such regions in vivo are varied and complex, data are emerging from genomic5–7 and protein8 analyses of endothelium at such sites that identify molecular differences. Some of these are accessible for study in vitro to investigate detailed mechanisms under more controlled conditions. …