Eating frequency is inversely associated with BMI, waist circumference and the proportion of body fat in Korean adults when diet quality is high, but not when it is low: analysis of the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV).

The role of eating frequency (EF) in obesity development has been debated, and few studies have investigated Asian populations. Diet quality might affect the association between EF and obesity. Therefore, we investigated the association between EF and obesity indicators in a representative sample of Korean adults with consideration to diet quality. This cross-sectional study used data of 6951 participants aged 19-93 years (male 49·8 %, female 50·2 %) from the Fourth Korean National Health and Nutrition Examination Survey. EF was assessed using a questionnaire, and diet quality was defined as mean adequacy ratio (MAR). To explore the association between EF and obesity indicators, we used multiple linear regression analyses with and without interaction terms between diet quality and EF. EF was inversely associated with each obesity indicator, including body fat percentage (BF%), BMI and waist circumference (WC), showing a significant linear trend (P<0·001 for BF%, WC and BMI). In addition, the association between EF and each obesity indicator was significantly altered according to diet quality (P value of the interaction term EF×diet quality=0·008 in the regression model for BF%, <0·001 for BMI and 0·043 for WC). In the stratified analyses according to diet quality, EF had a significant inverse association with BF%, WC and BMI in the high diet quality groups, but not in the low diet quality groups. This study suggests that EF is inversely associated with the obesity indicators when diet quality is high, but not when it is low in Korean adults.

Therapeutic application of T regulatory cells in composite tissue allotransplantation.

With growing number of cases in recent years, composite tissue allotransplantation (CTA) has been improving the quality of life of patient who seeks reconstruction and repair of damaged tissues. Composite tissue allografts are heterogeneous. They are composed of a variety of tissue types, including skin, muscle, vessel, bone, bone marrow, lymph nodes, nerve, and tendon. As a primary target of CTA, skin has high antigenicity with a rich repertoire of resident cells that play pivotal roles in immune surveillance. In this regard, understanding the molecular mechanisms involved in immune rejection in the skin would be essential to achieve successful CTA. Although scientific evidence has proved the necessity of immunosuppressive drugs to prevent rejection of allotransplanted tissues, there remains a lingering dilemma due to the lack of specificity of targeted immunosuppression and risks of side effects. A cumulative body of evidence has demonstrated T regulatory (Treg) cells have critical roles in induction of immune tolerance and immune homeostasis in preclinical and clinical studies. Presently, controlling immune susceptible characteristics of CTA with adoptive transfer of Treg cells is being considered promising and it has drawn great interests. This updated review will focus on a dominant form of Treg cells expressing CD4+CD25+ surface molecules and a forkhead box P3 transcription factor with immune tolerant and immune homeostasis activities. For future application of Treg cells as therapeutics in CTA, molecular and cellular characteristics of CTA and immune rejection, Treg cell development and phenotypes, Treg cell plasticity and stability, immune tolerant functions of Treg cells in CTA in preclinical studies, and protocols for therapeutic application of Treg cells in clinical settings are addressed in this review. Collectively, Treg cell therapy in CTA seems feasible with promising perspectives. However, the extreme high immunogenicity of CTA warrants caution.

Reinforcing Effects of Poly(D-Lactide)-g-Multiwall Carbon Nanotubes on Polylactide Nanocomposites.

Polylactide (PLA) nanocomposites with multi-walled carbon nanotubes (MWNTs) grafted with poly(L-lactide) or poly(D-lactide) were prepared by solution casting, and their thermal and mechanical properties were evaluated. MWNTs containing hydroxyl groups were treated by ring-opening polymerization of either L-lactide or D-lactide. Fourier transform infrared spectroscopy confirmed that the MWNT surfaces had been modified by the PLLA or PDLA chains. The thermal properties were measured by differential scanning calorimetry and thermogravimetric analysis. The mechanical properties were examined using a universal testing machine. The morphology of the fractured surfaces of the PLA nanocomposites was observed by scanning electron microscopy and transmission electron microscopy. PDLA-g-MWNTs were dispersed more uniformly compared to PLLA-g-MWNTs in the PLA matrix. The incorporation of PDLA-g-MWNTs greatly improved the tensile strength of the nanocomposites regardless of the contents. Thermal analysis revealed different characteristics at specific composites depending on the type of modification.

Mitral valve endothelial cells with osteogenic differentiation potential.

OBJECTIVE: Cardiac valvular endothelium is unique in its ability to undergo endothelial-to-mesenchymal transformation, a differentiation process that is essential for valve development and has been proposed as mechanism for replenishing the interstitial cells of mature valves. We hypothesized that the valvular endothelium contains endothelial cells that are direct precursors to osteoblastic valvular interstitial cells (VICs). METHODS AND RESULTS: Clonal cell populations from ovine mitral valve leaflets were isolated by single cell plating. Mitral valvular endothelial and mesenchymal clones were tested for osteogenic, adipogenic, and chondrogenic differentiation, determined by the expression of lineage-specific markers. Mitral valvular endothelial clones showed a propensity for osteogenic, as well as chondrogenic differentiation that was comparable to a mitral valvular VIC clone and to bone marrow-derived mesenchymal stem cells. Osteogenic differentiation was not detected in nonvalvular endothelial cells. Regions of osteocalcin expression, a marker of osteoblastic differentiation, were detected along the endothelium of mitral valves that had been subjected in vivo to mechanical stretch. CONCLUSIONS: Mitral valve leaflets contain endothelial cells with multilineage mesenchymal differentiation potential, including osteogenic differentiation. This unique feature suggests that postnatal mitral valvular endothelium harbors a reserve of progenitor cells that can contribute to osteogenic and chondrogenic VICs.

Discrepancy between participants' understanding and desire to know in informed consent: are they informed about what they really want to know?

BACKGROUND: Participants' understanding of clinical trials is important in informed consent. However, little is known about what information participants really want to know. AIMS: To demonstrate the existence of a discrepancy between participants' understanding and their desire to know. METHODS: The participants in clinical trials at Seoul National University Hospital were surveyed. The survey consisted of 11 statements based on the essential elements of informed consent. The participants gave two responses to each statement on a five-point Likert scale to rate their subjective understanding and desire to know, respectively. Information discrepancy was defined as the difference between these two ratings: if understanding exceeded desire to know for a particular item, it was defined as 'over-informed'; if desire to know exceeded understanding for a particular item, it was defined as 'under-informed'. RESULTS: Participants reported good understanding of 'voluntariness', 'duration', 'study involves research' and poor understanding of 'confidentiality', 'compensation', 'benefits', 'procedures' and 'risks or discomforts'. For 'risks or discomforts', 'who to contact', 'voluntariness', 'duration' and 'procedures', participants reported high desire to know compared with 'confidentiality', 'purpose', 'study involves research' and 'benefits'. The elements 'study involves research', 'voluntariness', 'duration', 'purpose' and 'who to contact' were over-informed, while 'compensation', 'risks or discomforts', 'procedures', 'confidentiality' and 'benefits' were under-informed. Participants over 50 years of age, those without a college education and those whose participation was less voluntary were relatively less informed about the clinical trials. CONCLUSIONS: An information discrepancy was observed between the participants' understanding and their desire to know. By putting more emphasis on under-informed elements, the quality of informed consent could be improved.

Proteomic analysis of human small cell lung cancer tissues: up-regulation of coactosin-like protein-1.

Small cell lung cancer (SCLC) is the leading cause of cancer death, with a high propensity for aggressiveness and metastasis even in an early stage. Thus, identification of biomarkers as early diagnostics and treatment is needed. In this study, we investigated differentially regulated proteins between human SCLC tissues and normal bronchial epithelium by proteomic analysis using two-dimensional electrophoresis (2-DE) and MALDI-TOF mass spectrometry. Seven proteins and protein isoforms, including, γ-actin, tubulin α-1B, laminin B1, coactosin-like protein-1 (COTL-1), ubiquitin carboxyl-terminal esterase L1, ubiquitin-conjugating enzyme E2-25K, and carbonic anhydrase 1, were up-regulated more than 2 fold in SCLC tissues. In particular, up-regulated COTL-1 expression was validated by Western blot analysis, immunohistochemistry, and reverse transcription quantitative polymerase chain reaction (RT-qPCR). Moreover, most SCLC tissues (93%; 28/30) were COTL-1-positive in immunohistochemistry, whereas only 16% (10/64) of nonsmall cell lung cancer (NSLC) tissues were. Taken together, this SCLC proteomic data may help in establishing a human SCLC proteome database. COTL-1 may be a biomarker or a therapeutic target in SCLC patients.

Association between scrub typhus encephalitis and diffusion tensor tractography detection of Papez circuit injury: A case report.

BACKGROUND: It is difficult to restore the cognitive functions of patients with impaired cognition caused by brain injury. Diffusion tensor imaging can visualize the integrity of neural tracts in the white matter (WM) three-dimensionally. It is unclear whether encephalitis following scrub typhus damages the WM. For the first time, we aimed to report diffusion tensor tractography (DTT) findings in a chronic patient with cognitive impairment following scrub typhus encephalitis, which revealed injury to the Papez circuit of the WM. CASE SUMMARY: A 70-year-old male patient was affected by encephalitis caused by scrub typhus that occurred 23 years ago. He had poor cognition and his clinical examination findings were as follows: Mini-Mental Status Examination score, 14; and handgrip strength (right/left, kg), 32.3/31.3. DTT revealed serious injuries of the left thalamocingulate tract and right mammillothalamic tract in the Papez circuit, and a partial injury of the anterior part of the fornix. CONCLUSION: Using DTT, we found a relationship between cognitive impairment and the integrity of the Papez circuit following scrub typhus.

Opposing actions of Notch1 and VEGF in post-natal cardiac valve endothelial cells.

The endothelium of the cardiac valves is unique compared the rest of the vasculature in its ability to undergo an endothelial-to-mesenchymal transformation (EMT) in vitro in response to transforming growth factor-beta (TGF-beta). EMT is a critical event during embryonic valve development, and both VEGF-A and Notch1 have been shown to function in this process. Here we investigate the effects of VEGF-A and Notch1 on EMT in clonal endothelial cell (EC) populations isolated from adult aortic valve leaflets. VEGF-A inhibited TGF-beta-induced EMT. Endothelial growth, however, was not affected by VEGF-A or TGF-beta. A positive role for Notch1 was revealed in three experiments: (1) TGF-beta induced Notch1 mRNA in valve ECs, (2) a gamma-secretase inhibitor of Notch1 signaling blocked EMT, and (3) overexpression of a ligand-independent form of Notch1 induced EMT. These results demonstrate, for the first time, that VEGF-A and Notch1 play opposing roles in regulating EMT in post-natal valve endothelium.

Human pulmonary valve progenitor cells exhibit endothelial/mesenchymal plasticity in response to vascular endothelial growth factor-A and transforming growth factor-beta2.

In situ analysis of fetal semilunar valve leaflets has revealed cells coexpressing endothelial and mesenchymal markers along the endothelium, with diminished frequency seen in adult valves. To determine whether such cells are progenitor cells, we isolated clonal populations from human pulmonary valves. The clones expressed endothelial markers but showed potential to further differentiate into endothelium in response to vascular endothelial growth factor (VEGF)-A. When exposed to transforming growth factor (TGF)-beta2, individual clones adopted a mesenchymal phenotype to varying degrees and expressed markers of endothelial to mesenchymal transformation (EMT). Both VEGF- and TGFbeta2-induced phenotypic changes were partially reversible, indicating the plasticity of these cells. When challenged with VEGF or TGFbeta2, a hierarchy of endothelial/mesenchymal potential could be seen among the clonal populations: cells initially closer to an endothelial phenotype showed a strong response to TGFbeta2 that could be inhibited by VEGF, whereas cells closer to a mesenchymal phenotype responded to TGFbeta2 but were resistant to endothelial-inducing effects of VEGF. These findings suggest the presence of bipotential valve progenitor cells with ability to differentiate into either endothelial or interstitial cells of the valve leaflet. Understanding the differentiation potential and function of these cells may be important for understanding heart valve disease and may also be applied to current paradigms for creating tissue-engineered heart valves.

Mechanism of cognitive impairment in chronic patients with putaminal hemorrhage: A diffusion tensor tractography.

It is not clear whether the fornix and cingulum are involved in cognition after putaminal hemorrhage (PH). We investigated structural changes and differences of the neural tracts, and the relationship between the integrity of the neural tracts and cognition not only at the affected but also at the unaffected side.Sixteen patients with left chronic putaminal hemorrhage and 20 healthy volunteers were enrolled. Using diffusion tensor tractography (DTT), we compared fiber number (FN), fractional anisotropy (FA), and apparent diffusion coefficient (ADC) of the neural tracts between patient and control groups. The relationship between the neural tract parameters and neuropsychological results was also analyzed.The left fornix FN was significantly lower than the right fornix FN in the patient group. Except for the cingulum FA, the neural tracts parameters for both the affected and unaffected hemispheres differed significantly between the groups. The fornix FA and ADC at the affected side were significantly correlated with intelligence quotient (IQ), mini-mental status examination (MMSE), and short-term memory. Interestingly, the fornix ADC at the unaffected side was significantly correlated with MMSE. However, none of the cingulum parameters was correlated with neuropsychological results.The fornix integrity is critical for cognitive impairment after putaminal hemorrhage.

Development of a Modified Korean East Asian Student Stress Inventory by Comparing Stress Levels in Medical Students with Those in Non-Medical Students.

BACKGROUND: Medical students are usually under more stress than that experienced by non-medical students. Stress testing tools for Korean medical students have not been sufficiently studied. Thus, we adapted and modified the East Asian Student Stress Inventory (EASSI), a stress testing tool for Korean students studying abroad, and verified its usefulness as a stress test in Korean university students. We also compared and analyzed stress levels between medical and non-medical students. METHODS: A questionnaire survey was conducted on medical and non-medical students of a national university, and the responses of 224 students were analyzed for this study. Factor analysis and reliability testing were performed based on data collected for 25 adapted EASSI questions and those on the Korean version of the Global Assessment of Recent Stress Scale (GARSS). A correlation analysis was performed between the 13 modified EASSI questions and the GARSS, and validity of the modified EASSI was verified by directly comparing stress levels between the two student groups. RESULTS: The 13 questions adapted for the EASSI were called the modified EASSI and classified into four factors through a factor analysis and reliability testing. The Pearson's correlation analysis revealed a significant correlation between the modified EASSI and the Korean version of the GARSS, suggesting a complementary strategy of using both tests. CONCLUSION: The validity and reliability of the EASSI were verified. The modified Korean EASSI could be a useful stress test for Korean medical students. Our results show that medical students were under more stress than that of non-medical students. Thus, these results could be helpful for managing stress in medical students.

North Korean refugee doctors' preliminary examination scores.

PURPOSE: Although there have been studies emphasizing the re-education of North Korean (NK) doctors for post-unification of the Korean Peninsula, study on the content and scope of such re-education has yet to be conducted. Researchers intended to set the content and scope of re-education by a comparative analysis for the scores of the preliminary examination, which is comparable to the Korean Medical Licensing Examination (KMLE). METHODS: The scores of the first and second preliminary exams were analyzed by subject using the Wilcoxon signed rank test. The passing status of the group of NK doctors for KMLE in recent 3 years were investigated. The multiple-choice-question (MCQ) items of which difficulty indexes of NK doctors were lower than those of South Korean (SK) medical students by two times of the standard deviation of the scores of SK medical students were selected to investigate the relevant reasons. RESULTS: The average scores of nearly all subjects were improved in the second exam compared with the first exam. The passing rate of the group of NK doctors was 75%. The number of MCQ items of which difficulty indexes of NK doctors were lower than those of SK medical students was 51 (6.38%). NK doctors' lack of understandings for Diagnostic Techniques and Procedures, Therapeutics, Prenatal Care, and Managed Care Programs was suggested as the possible reason. CONCLUSION: The education of integrated courses focusing on Diagnostic Techniques and Procedures and Therapeutics, and apprenticeship-style training for clinical practice of core subjects are needed. Special lectures on the Preventive Medicine are likely to be required also.

Multiple mini-interviews as a predictor of academic achievements during the first 2 years of medical school.

BACKGROUND: Recently, conventional interviews have been replaced with the multiple mini-interviews (MMI) for medical student selection in Korea. We first introduced the MMI as a new admissions tool in Korea. The aim of this study is to determine whether the MMI accurately predicts academic achievement on both written and performance-based examinations during the first 2 years of medical school. METHODS: The original scores of each station were standardized to T-scores in the candidates group. Three cohorts of students were included depending upon the year they entered medical school. Pearson's correlations were calculated to estimate the correlations between MMI scores and academic achievements. Additional correlated factors were run through multiple stepwise linear regression analysis to estimate predictive validity. RESULTS: There were no differences between T-scores or grade point averages (GPA) among the cohorts. The correlation coefficients between total MMI scores and academic achievement in Year 1 and the Year 2 performance-based examinations ranged from 0.17 to 0.43. Station 1 significantly predicted academic achievement over the second year. Station 3 significantly predicted only performance-based examination performance over the second year. CONCLUSION: MMI is a useful tool to assist with medical student selection. In particular, critical thinking, professionalism, and presentation and communication skills may be meaningful topics for predicting academic achievements, especially in performance-based subjects.

Anatomical location and somatotopic organization of the corticospinal tract in the corona radiata of the normal human brain: a diffusion tensor tractography study.

The anatomical location and somatotopic organization of the corticospinal tract (CST) in the corona radiata (CR) of the normal human brain have not been studied using diffusion tensor tractography so far. In this study, the anatomical location and somatotopic organization of the CST in the CR were evaluated by determining the highest probabilistic locations and distances between the upper and lower extremities in the slices of upper and lower CR in the brain. In the mediolateral direction, the average of the highest probabilistic locations for the upper and lower extremities were 40.27 and 37.16% at the upper CR level and 38.19 and 37.14% at the lower CR level, respectively. In the anteroposterior direction, the average of the highest probabilistic locations for the upper and lower extremities were 62.52 and 75.65% at the upper CR level and 60.19 and 68.12% at the lower CR level, respectively. The average distances between upper and lower extremities for the mediolateral direction were 2.41 mm at the upper CR level and 1.21 mm at the lower CR level. The average distances between upper and lower extremities for the anteroposterior direction were 5.23 mm at the upper CR level and 4.47 mm at the lower CR level, respectively. Our findings suggest that the anatomical location and somatotopic organization for the upper extremity are located anterolaterally to the lower extremity in the CR of a normal human brain and distances between the upper and lower extremities become decreased as the CST descends from the upper to the lower CR level.

Lipoprotein-associated phospholipase A2 is related to plaque stability and is a potential biomarker for acute coronary syndrome.

PURPOSE: Plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) binds to low-density lipoprotein. The levels of Lp-PLA2 reflect the plaque burden, and are upregulated in acute coronary syndrome (ACS). We investigated the diagnostic value of Lp-PLA2 levels and found that it might be a potential biomarker for ACS. MATERIALS AND METHODS: We classified 226 study participants into three groups: patients without significant stenosis (control group), patients with significant stenosis with stable angina (SA group), and patients with ACS (ACS group). RESULTS: Lp-PLA2 and high-sensitivity C-reactive protein (hs-CRP) levels were significantly greater in the ACS group than in the SA group (p=0.044 and p=0.029, respectively). Multivariate logistic regression analysis revealed that Lp-PLA2 levels are significantly associated with ACS (odds ratio=1.047, p=0.013). The addition of Lp-PLA2 to the ACS model significantly increased the global χ² value over traditional risk factors (28.14 to 35.602, p=0.006). The area under the receiver operating characteristic curve for Lp-PLA2 was 0.624 (p=0.004). The addition of Lp-PLA2 level to serum hs-CRP concentration yielded an integrated discrimination improvement of 0.0368 (p=0.0093, standard error: 0.0142) and improved the ability to diagnose ACS. CONCLUSION: Lp-PLA2 levels are related to plaque stability and might be a diagnostic biomarker for ACS.

Characterization of the cytokine profile of platelet rich plasma (PRP) and PRP-induced cell proliferation and migration: Upregulation of matrix metalloproteinase-1 and -9 in HaCaT cells.

BACKGROUND: The underlying rationale of platelet rich plasma (PRP) therapy is that an injection of concentrated PRP at the site of injury may promote tissue repair via cytokine release from platelets. The molecular mechanisms of PRP therapy in the skin wound healing process are not well understood at present, and would benefit from clarification. METHODS: PRP was stimulated with angonists for 5 min, and cytokine profile analysis was performed. To investigate the wound healing activity of PRP, cell proliferation and migration analyses were performed in skin cells. The effects of PRP were analyzed on the expression and activity of matrix metalloproteinase (MMP)-1, -2, -9, and the activation of transcription factors. RESULTS: Thrombin was found to be a strong stimulator of PRP activation to release growth factors and chemokines. PRP induced cell proliferation and migration in HUVECs, HaCaT cells, and HDFs, as well as MMP-1and MMP-9 expression in HaCaT cells, but PRP did not have a significant effect on the expression or activity of MMPs in HDFs. The transcription factors, including signal transducer and activator of transcription-3 (STAT-3) were found to be phosphorylated following PRP treatment in HaCaT cells. CONCLUSION: In this study, we have identified the cytokine profile of activated PRP after agonist stimulation. We have shown that PRP plays an active role in promoting the proliferation and migration of skin cells via the regulation of MMPs, and this may be applicable to the future development of PRP therapeutics to enhance skin wound healing.

Implementation of a Videoconferencing System between Multiple Family Medicine Departments.

Attending conferences is important for doctors and residents in family medicine. Nevertheless, departments of family medicine at many hospitals find it difficult to hold regular conferences. Holding joint videoconferences between Family Medicine Departments of several hospitals through a videoconferencing system could solve this problem. Therefore, Family Medicine Departments of Seoul National University Hospital, Seoul National University Bundang Hospital, and Kangwon National University Hospital decided to hold regular joint videoconferences via a videoconferencing system. Eighty-one joint videoconferences were held from April 1 to October 29, 2010. PowerPoint slideshows were transferred to the other two locations in the same resolution as presenter's monitor. Image and voice of the speaker were transferred in real time and in acceptable quality. Joint videoconferences are feasible, satisfactory and useful for medical education, especially when individual family medicine departments are small and lack resources to hold face-to-face conferences. We expect that more family medicine departments will choose to participate in implementing similar joint videoconferencing systems in the future.

Homoisoflavanone inhibits UVB-induced skin inflammation through reduced cyclooxygenase-2 expression and NF-kappaB nuclear localization.

BACKGROUND: Since the generation of reactive oxygen species (ROS) and release of inflammatory mediators play a major role in UVB-induced inflammation, vigorous attempts have been made for the pharmacological management of these molecules as well as for uncovering the molecular signaling pathways. Homoisoflavanone (5,7-dihydroxy-3-(3-hydroxy-4-methoxybenzyl)-chroman-4-one, HIF) extracted from Cremastra appendiculata has anti-angiogenic activities, but its effect on inflammation was unknown. OBJECTIVE: To investigate the anti-inflammatory effects of HIF on the skin and the underlying molecular mechanisms. METHODS: HaCaT cells were irradiated by UVB (10 mJ/cm(2)) with or without HIF. Prostaglandin E(2) (PGE(2)) level was measured by enzyme immunoassay. Activation of MAPK and production of cyclooxygenase-2 (COX-2) were determined by Western blot analysis. Localization of nuclear factor kappa B (NF-kappaB) was assessed by immunofluorescence microscopy. Hairless mice were stimulated with UVB or chemical stimulants to induce inflammatory responses in skin. RESULTS: Pretreatment with HIF inhibited the production of intracellular ROS induced by UVB irradiation in HaCaT cells. Further analysis revealed a decrease in the level of MAPK activation and down-regulation of COX-2 expression. In addition, HIF attenuated the nuclear localization of NF-kappaB, resulting in the suppression of inflammatory molecules such as IL-6, IL-8, and TNF-alpha. Finally, topical treatment with HIF inhibited ear edema induced by UVB, 12-O-tetradecanoylphorbol-13-acetate (TPA), arachidonic acid (AA), or croton oil. CONCLUSION: HIF has a strong protective effect against proinflammatory responses, implying the possibility of preventive application for inflammatory skin diseases.

Differential functions of genes regulated by VEGF-NFATc1 signaling pathway in the migration of pulmonary valve endothelial cells.

We have reported that vascular endothelial growth factor (VEGF)-A induces the proliferation of human pulmonary valve endothelial cells (HPVECs) through nuclear factor in activated T cells (NFAT)c1 activation. Here we show that VEGF-A increases the migration of HPVECs through NFATc1 activation, suggesting that VEGF-A/NFATc1 regulates the migration of HPVECs. To learn how this pathway may be involved in post-natal valvular repair, HPVECs were treated with VEGF-A, with or without cyclosporine A to selectively block VEGF-NFATc1 signaling. Down Syndrome critical region 1 (DSCR1) and heparin-binding EGF-like growth factor (HB-EGF) are two genes identified by DNA microarray as being up-regulated by VEGF-A in a cyclosporine-A-sensitive manner. DSCR1 silencing increased the migration of ovine valve endothelial cells, whereas HB-EGF silencing inhibited migration. This differential effect suggests that VEGF-A/NFATc1 signaling might be a crucial coordinator of endothelial cell migration in post-natal valves.