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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.

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 (PPvalue of the interaction term EF×diet quality=0·008 in the regression model for BF%

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.

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.

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.

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.

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.

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.

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)-β 2 , individual clones adopted a mesenchymal phenotype to varying degrees and expressed markers of endothelial to mesenchymal transformation (EMT). Both VEGF- and TGFβ 2 –induced phenotypic changes were partially reversible, indicating the plasticity of these cells. When challenged with VEGF or TGFβ 2 , 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 TGFβ 2 that could be inhibited by VEGF, whereas cells closer to a mesenchymal phenotype responded to TGFβ 2 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.

This study was done to verify the validity and the reliability of the newly developed Computerized Dementia Screening Test (CDST) to be easily used in the primary care setting of Korea.Comparison of the results of CDST between 103 healthy control subjects and 41 patients who were diagnosed as having mild cognitive impairment or early dementia, having a clinical dementia rate of 0.5-1 from one health examination center and two neurology clinics in university hospitals.In order to estimate the criterion-related validity, logistic regression analysis for dementia was done using the four individual test results of CDST, age and educational level. The correlation between Korean Mini-Mental State Examination (K-MMSE) and the predicted probability of mild cognitive impairment and early dementia from the logistic regression was measured to verify its validity. The reliability of CDST was measured by test-retest reliability.The sensitivity and specificity of CDST were 75.6% and 94.2%, respectively, if the cut-off point was set to be 0.5 in the logistic regression model. The Pearson's Correlation Coefficient between K-MMSE and the predicted probability of mild cognitive impairment and early dementia from the logistic regression analysis was 0.59 (P0.001). The overall test-retest reliability using the predicted probability of dementia from the logistic regression analysis of CDST was 0.89 (P=0.01).The validity and reliability of CDST is adequate for use as a screening tool to identify mild cognitive impairment and early dementia in Korean primary care.

When the monocyte infiltrates a tissue, adhesion to the extracellular matrix provides structural anchors, and the cell may be deformed through these attachments. To test the hypothesis that human monocytes/macrophages are mechanically responsive, we studied the effects of small cyclic mechanical deformations on cultured human monocytes/macrophages. When monocytes/macrophages were subjected to 4% strain at 1 Hz for 24 hours, neither matrix metalloproteinase (MMP)-1 nor MMP-3 was induced; however, in the presence of phorbol myristate acetate, strain augmented MMP-1 expression by 5.1 ± 0.7-fold (P < 0.05) and MMP-3 expression by 1.6 ± 0.1-fold (P < 0.05). In contrast, MMP-9 expression was not changed by mechanical strain in the presence or absence of phorbol myristate acetate. Deformation rapidly induced the immediate early response genes c-fos and c-jun. In addition, mechanical deformation induced the transcription factor PU.1, an ets family member that is essential in monocyte differentiation, as well as mRNA for the M-CSF receptor. These studies demonstrate that human monocytes/macrophages respond to mechanical deformation with selective augmentation of MMPs, induction of immediate early genes, and induction of the M-CSF receptor. In addition to enhancing the proteolytic activity of macrophages within repairing tissues, cellular deformation within tissues may play a role in monocyte differentiation.

Mechanical forces and biochemical stimuli may interact to regulate cellular responses. In this study, we tested the hypothesis that very small mechanical strains interact with growth factors in the regulation of matrix metalloproteinase (MMP)-1. Human vascular smooth muscle cells (VSMCs) were cultured on a precoated silicone membrane in a device that imposes a highly uniform biaxial strain. VSMCs cultured on fibronectin were treated with cyclic 1-Hz strains of 0, 1, or 4%, and MMPs were assayed by Western analysis or gelatin zymography. Small strains did not induce MMP-1 in VSMCs, but strain was a potent inhibitor of platelet-derived growth factor (PDGF)- or tumor necrosis factor-alpha-induced synthesis of MMP-1. In contrast, MMP-2 and TIMP-2 levels were not changed by PDGF and/or mechanical strain. VSMCs strained on the 120-kDa chymotryptic fragment of fibronectin or RGD peptides suppressed PDGF-induced expression of MMP-1, indicating that this effect is not mediated by the heparin-binding domain or connecting segment-1 of fibronectin. Northern analysis of ets-1, a transcriptional activator of MMP-1 expression, showed that strain down-regulated ets-1 expression, whereas c-fos expression was augmented. Thus, small deformations can selectively suppress MMP-1 synthesis by VSMCs, demonstrating the exquisite sensitivity of the cell to mechanical stimuli.

Background Participants9 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 participants9 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 participants9 understanding and their desire to know. By putting more emphasis on under-informed elements, the quality of informed consent could be improved.

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-κB) 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-κB, resulting in the suppression of inflammatory molecules such as IL-6, IL-8, and TNF-α. 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.

Capsiate, one of the major capsaicinoids, is nonpungent and present in sweet pepper. We investigated the effects of capsiate on the ultraviolet B (UVB)-induced inflammatory response in skin and its molecular mechanisms. Capsiate-pretreated human keratinocytes inhibited intracellular reactive oxygen species (ROS), which activate the mitogen-activated protein kinase and nuclear factor-kappaB (NF-kappaB) pathways. Therefore, we determined the effects of capsiate on these pathways. Capsiate inhibited UVB-induced cyclooxygenase-2 (COX-2) expression, extracellular signal-related kinase 1/2 phosphorylation, nuclear translocation of NF-kappaB, and the expression of proinflammatory cytokines and potent angiogenic factors, including vascular endothelial cell growth factor and matrix metalloproteinase-2 (MMP-2) and MMP-9. In addition, capsiate inhibited UVB-induced epidermal growth factor receptor (EGFR) activation, which reduces the levels of proinflammatory cytokines and angiogenic factors. We also investigated the photoprotective effects of capsiate in vivo. Topical treatment with capsiate significantly decreased UVB-induced skin damage and inhibited the expression of COX-2, proinflammatory cytokines, and angiogenic factors, including platelet/endothelial cell adhesion molecule-1 and intercellular adhesion molecule-1. Inhibition of Src kinase activity and ROS may inhibit the EGFR activation. Therefore, capsiate may protect the skin from UVB-induced adverse effects and these results provide a molecular basis for understanding its effects on inflammation and angiogenesis.

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 [1]. 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.

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.

The goal of this study is to measure women's willingness to pay for cancer screening and to identify those factors associated with this willingness to payA population-based telephone survey was performed on 1,562 women (aged 30 years or over) for 2 weeks (9-23th, July, 2004). Data about sociodemographic characteristics, health behaviors, the intention of the cancer screenings and willingness to pay for cancer screening were collected. 1,400 respondents were included in the analysis. The women's willingness to pay for cancer screening and the factors associated with this willingness to pay were evaluated.The results show that 76% of all respondents have a willingness to pay for cancer screening. Among those who are willing to pay, the average and median amount of money for which the respondents are willing to pay are 126,636 (s.d.: 58,414) and 120,000 won, respectively. As the status of educationthe income are higher, the average amount that women are willing to pay becomes much more. The amount of money women are willing to pay is the highest during the 'contemplation' stage. Being willing to pay or not is associated with a change of behavior (transtheoretical model), the income, the concern about the cancer risk, the family cancer history, the marital status, the general health exam, age and the place of residence. Income is associated with a greater willingness to pay. Old age was associated with a lower willingness to pay.According to the two-part model, income and TTM are the most important variables associated with the willingness to pay for cancer screening. The cancer screening participation rate is low compared with the willingness to pay for cancer screening. It is thought that we have to consider the participants' behavior that's associated with cancer screening and their willingness to pay in order to organize and manage cancer screening program.

Tumor necrosis factor (TNF) receptor-associated factor (TRAF) 2 is an intracellular adapter protein, which, upon TNF stimulation, is directly recruited to the intracellular region of TNF receptor 2 (TNFR2) or indirectly, via TRADD, to the intracellular region of TNF receptor 1 (TNFR1). In cultured human umbilical vein endothelial cells, endogenous TRAF2 colocalizes with the membrane-organizing protein caveolin-1 at regions of enrichment subjacent to the plasma membrane as detected by confocal fluorescence microscopy. Both endogenous and transfected TRAF2 protein coimmunoprecipitate with caveolin-1 in the absence of ligand. Upon TNF treatment, the TRAF2-caveolin-1 complex transiently associates with TRADD, and upon overexpression of TNFR2, the TRAF2-caveolin-1 complex stably associates with and causes redistribution of this receptor as detected by confocal fluorescence microscopy. In human embryonic kidney 293 cells, which have minimal endogenous expression of caveolin-1, cotransfection of TRAF2 and caveolin-1 results in spontaneous association of these proteins which can further associate with and redistribute transfected TNFR2 molecules. The association of caveolin-1 with TNFR2 depends upon TRAF2. Cotransfection of caveolin-1 protein increases TRAF2 protein expression levels in HEK 293 cells, which correlates with enhancement of TNF and TRAF2 signaling, measured as transcription of a NF-kappaB promoter-reporter gene, although the caveolin-enhanced response to TNF is attenuated at higher caveolin levels. These findings suggest that intracellular distribution of activated TNF receptors may be regulated by caveolin-1 via its interaction with TRAF2.

Background —Unstable atherosclerotic lesions typically have an abundant inflammatory cell infiltrate, including activated T cells, macrophages, and mast cells, which may decrease plaque stability. The pathophysiology of inflammatory cell recruitment and activation in the human atheroma is incompletely described. Methods and Results —We hypothesized that differential gene expression with DNA microarray technology would identify new genes that may participate in vascular inflammation. RNA isolated from cultured human aortic smooth muscle cells treated with tumor necrosis factor-α (TNF-α) was examined with a DNA microarray with 8600 genes. This experiment and subsequent Northern analyses demonstrated marked increases in steady-state eotaxin mRNA (>20 fold), a chemokine initially described as a chemotactic factor for eosinophils. Because eosinophils are rarely present in human atherosclerosis, we then studied tissue samples from 7 normal and 14 atherosclerotic arteries. Immunohistochemical analysis demonstrated overexpression of eotaxin protein and its receptor, CCR3, in the human atheroma, with negligible expression in normal vessels. Eotaxin was predominantly located in smooth muscle cells. The CCR3 receptor was localized primarily to macrophage-rich regions as defined by immunopositivity for CD 68; a minority of mast cells also demonstrated immunopositivity for the CCR3 receptor. Conclusions —Eotaxin and its receptor, CCR3, are overexpressed in human atherosclerosis, suggesting that eotaxin participates in vascular inflammation. These data demonstrate how genomic differential expression technology can identify novel genes that may participate in the stability of atherosclerotic lesions.

Abstract —Vascular smooth muscle cells must monitor and respond to their mechanical environment; however, the molecular response of these cells to mechanical stimuli remains incompletely defined. By applying a highly uniform biaxial cyclic strain to cultured cells, we used DNA microarray technology to describe the transcriptional profile of mechanically induced genes in human aortic smooth muscle cells. We first identified vascular endothelial growth factor (VEGF) as a mechanically induced gene in these cells; VEGF served as a positive control for these experiments. We then used a DNA microarray with 5000 genes with putative functions to identify additional mechanically induced genes. Surprisingly, relatively few genes are mechanically induced in human aortic smooth muscle cells. Only 3 transcripts of 5000 were induced >2.5-fold: cyclooxygenase-1, tenascin-C, and plasminogen activator inhibitor-1. Downregulated transcripts included matrix metalloproteinase-1 and thrombomodulin. The transcriptional profile of mechanically induced genes in human aortic smooth muscle cells suggests a response of defense against excessive deformation. These data also demonstrate that in addition to identifying large clusters of genes that respond to a given stimulus, DNA microarray technology may be used to identify a small subset of genes that comprise a highly specific molecular response.