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| 1 | Delayed gastric emptying following pancreaticoduodenectomy:Incidence,risk factors,and healthcare utilization显示文摘AIM To characterize incidence and risk factors for delayed gastric emptying(DGE) following pancreaticoduodenectomy and examine its implications on healthcare utilization. METHODS A prospectively-maintained database was reviewed. DGE was classified using International Study Group of Pancreatic Surgery criteria. Patients who developed DGE and those who did not were compared. RESULTS Two hundred and seventy-six patients underwent pancreaticoduodenectomy(PD)(> 80% pyloruspreserving, antecolic-reconstruction). DGE developed in 49 patients(17.8%): 5.1% grade B, 3.6% grade C. Demographic, clinical, and operative variables were similar between patients with DGE and those without. DGE patients were more likely to present multiplecomplications(32.6% vs 4.4%, ≥ 3 complications, P < 0.001), including postoperative pancreatic fistula(POPF)(42.9% vs 18.9%, P = 0.001) and intra-abdominal abscess(IAA)(16.3% vs 4.0%, P = 0.012). Patients with DGE had longer hospital stay(median, 12 d vs 7 d, P < 0.001) and were more likely to require transitional care upon discharge(24.5% vs 6.6%, P < 0.001). On multivariate analysis, predictors for DGE included POPF [OR = 3.39(1.35-8.52), P = 0.009] and IAA [OR = 1.51(1.03-2.22), P = 0.035].CONCLUSION Although DGE occurred in < 20% of patients after PD, it was associated with increased healthcare utilization. Patients with POPF and IAA were at risk for DGE. Anticipating DGE can help individualize care and allocate resources to high-risk patients. | Somala Mohammed George Van Buren II Amy Mc Elhany Eric J Silberfein William E Fisher | 2017 | World Journal of Gastrointestinal Surgery2017，9，3： | 13 |
| 2 | Predictors of suboptimal bowel preparation in asymptomatic patients undergoing average-risk screening colonoscopy显示文摘AIM To identify risk factors for a suboptimal preparation among a population undergoing screening or surveillance colonoscopy.METHODS Retrospective review of the University of Michigan and Veteran's Administration(VA) Hospital records from 2009 to identify patients age 50 and older who underwent screening or surveillance procedure and had resection of polyps less than 1 cm in size and no more than 2 polyps. Patients with inflammatory bowel disease or a family history of colorectal cancer were excluded. Suboptimal procedures were defined as procedure preparations categorized as fair, poor or inadequate by the endoscopist. Multivariable logistic regression was used to identify predictors of suboptimal preparation.RESULTS Of 4427 colonoscopies reviewed, 2401 met our inclusion criteria and were analyzed. Of our population, 16% had a suboptimal preparation. African Americans were 70% more likely to have a suboptimal preparation(95%CI: 1.2-2.4). Univariable analysis revealed that narcotic and tricyclic antidepressants(TCA) use, diabetes, prep type, site(VA vs non-VA), and presence of a gastroenterology(GI) fellow were associated with suboptimal prep quality. In a multivariable model controlling for gender, age, ethnicity, procedure site and presence of a GI fellow, diabetes [odds ratio(OR) = 2.3; 95%CI: 1.6-3.2], TCA use(OR = 2.5; 95%CI: 1.3-4.9), narcotic use(OR = 1.7; 95%CI: 1.2-2.5) and Miralax-Gatorade prep vs 4L polyethylene glycol 3350(OR = 0.6; 95%CI: 0.4-0.9) were associated with a suboptimal prep quality. CONCLUSION Diabetes, narcotics use and TCA use were identified as predictors of poor preparation in screening colonoscopies while Miralax-Gatorade preps were associated with better bowel preparation. | Shail M Govani Eric E Elliott Stacy B Menees Stephanie L Judd Sameer D Saini Constantinos P Anastassiades Annette L Urganus Suzanna J Boyce Philip S Schoenfeld | 2016 | World Journal of Gastrointestinal Endoscopy2016，8，17： | 7 |
| 3 | Selecting suitable solid organ transplant donors: Reducing the risk of donor-transmitted infections显示文摘Selection of the appropriate donor is essential to a successful allograft recipient outcome for solid organ transplantation. Multiple infectious diseases have been transmitted from the donor to the recipient via transplantation. Donor-transmitted infections cause increased morbidity and mortality to the recipient. In recent years, a series of high-profile transmissions of infections have occurred in organ recipients prompt-ing increased attention on the process of improving the selection of an appropriate donor that balances the shortage of needed allografts with an approach that mitigates the risk of donor-transmitted infection to the recipient. Important advances focused on improving donor screening diagnostics, using previously excluded high-risk donors, and individualizing the selection of allografts to recipients based on their prior infection history are serving to increase the donor pool and improve outcomes after transplant. This article serves to review the relevant literature surrounding this topic and to provide a suggested approach to the selection of an appropriate solid organ transplant donor. | Christopher S Kovacs Jr Christine E Koval David van Duin Amanda Guedes de Morais Blanca E Gonzalez Robin K Avery Steven D Mawhorter Kyle D Brizendine Eric D Cober Cyndee Miranda Rabin K Shrestha Lucileia Teixeira Sherif B Mossad | 2014 | World Journal of Transplantation2014，4，2： | 7 |
| 4 | High-density SNP-based genetic maps for the parents of an outcrossed and a selfed tetraploid garden rose cross, inferred from admixed progeny using the 68k rose SNP array显示文摘Dense genetic maps create a base for QTL analysis of important traits and future implementation of marker-assisted breeding.In tetraploid rose,the existing linkage maps include<300 markers to cover 28 linkage groups(4 homologous sets of 7 chromosomes).Here we used the 68k WagRhSNP Axiom single-nucleotide polymorphism(SNP)array for rose,in combination with SNP dosage calling at the tetraploid level,to genotype offspring from the garden rose cultivar‘Red New Dawn’.The offspring proved to be not from a single bi-parental cross.In rose breeding,crosses with unintended parents occur regularly.We developed a strategy to separate progeny into putative populations,even while one of the parents was unknown,using principle component analysis on pairwise genetic distances based on sets of selected SNP markers that were homozygous,and therefore uninformative for one parent.One of the inferred populations was consistent with self-fertilization of‘Red New Dawn’.Subsequently,linkage maps were generated for a bi-parental and a self-pollinated population with‘Red New Dawn’as the common maternal parent.The densest map,for the selfed parent,had 1929 SNP markers on 25 linkage groups,covering 1765.5 cM at an average marker distance of 0.9 cM.Synteny with the strawberry(Fragaria vesca)genome was extensive.Rose ICM1 corresponded to F.vesca pseudochromosome 7(Fv7),ICM4 to Fv4,ICM5 to Fv3,ICM6 to Fv2 and ICM7 to Fv5.Rose ICM2 corresponded to parts of F.vesca pseudochromosomes 1 and 6,whereas ICM3 is syntenic to the remainder of Fv6. | Mirjana Vukosavljev Paul Arens Roeland E Voorrips Wendy P C van't Westende G D Esselink Peter M Bourke Peter Cox W Eric van de Weg Richard G F Visser Chris Maliepaard Marinus J M Smulders | 2016 | Horticulture Research2016，3，1： | 6 |
| 5 | Colonoscopic yield of colorectal neoplasia in daily clinical practice显示文摘AIM:To assess the prevalence and location of ad-vanced neoplasia in patients undergoing colonoscopy,and to compare the yield per indication.METHODS:In a multicenter colonoscopy survey (n = 18 hospitals) in the Amsterdam area (Northern Holland),data of all colonoscopies performed during a three month period in 2005 were analyzed. The location and the histological features of all colonic neoplasia were recorded. The prevalence and the distribution ofadvanced colorectal neoplasia and differences in yield between indication clusters were evaluated. Advanced neoplasm was defi ned as adenoma > 10 mm in size,with > 25% villous features or with high-grade dyspla-sia or cancer.RESULTS:A total of 4623 eligible patients underwent a total colonoscopy. The prevalence of advanced neo-plasia was 13%,with 281 (6%) adenocarcinomas and 342 (7%) advanced adenomas. Sixty-seven percent and 33% of advanced neoplasia were located in the distal and proximal colon,respectively. Of all patients with right-sided advanced neoplasia (n = 228),51% had a normal distal colon,whereas 27% had a syn-chronous distal adenoma. Ten percent of all colono-scopies were performed in asymptomatic patients,7% of whom had advanced neoplasia. In the respective procedure indication clusters,the prevalence of right-sided advanced neoplasia ranged from 11%-57%. CONCLUSION:One out of every 7-8 colonoscopies yielded an advanced colorectal neoplasm. Colonoscopy is warranted for the evaluation of both symptomatic and asymptomatic patients. | Jochim S Terhaar sive Droste Mike E Craanen Rene WM van der Hulst Joep F Bartelsman Dick P Bezemer Kim R Cappendijk Gerrit A Meijer Linde M Morsink Pleun Snel Hans ARE Tuynman Roy LJ van Wanrooy Eric IC Wesdorp Chris JJ Mulder | 2009 | World Journal of Gastroenterology2009，15，9： | 6 |
| 6 | Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial显示文摘 | Eric Lawitz Fred F Poordad Phillip S Pang Robert H Hyland Xiao Ding Hongmei Mo William T Symonds John G McHutchison Fernando E Membreno | 2013 | The Lancet2013，，： | 5 |
| 7 | Miniature gastrointestinal endoscopy: Now and the future显示文摘Since its original application,gastrointestinal(GI)endoscopy has undergone many innovative transformations aimed at expanding the scope,safety,accuracy,acceptability and cost-effectiveness of this area of clinical practice.One method of achieving this has been to reduce the caliber of endoscopic devices.We propose the collective term“Miniature GI Endoscopy”.In this Opinion Review,the innovations in this field are explored and discussed.The progress and clinical use of the three main areas of miniature GI endoscopy(ultrathin endoscopy,wireless endoscopy and scanning fiber endoscopy)are described.The opportunities presented by these technologies are set out in a clinical context,as are their current limitations.Many of the positive aspects of miniature endoscopy are clear,in that smaller devices provide access to potentially all of the alimentary canal,while conferring high patient acceptability.This must be balanced with the costs of new technologies and recognition of device specific challenges.Perspectives on future application are also considered and the efforts being made to bring new innovations to a clinical platform are outlined.Current devices demonstrate that miniature GI endoscopy has a valuable place in investigation of symptoms,therapeutic intervention and screening.Newer technologies give promise that the potential for enhancing the investigation and management of GI complaints is significant. | John J McGoran Mark E McAlindon Prasad G Iyer Eric J Seibel Rehan Haidry Laurence B Lovat Sarmed S Sami | 2019 | World Journal of Gastroenterology2019，25，30： | 4 |
| 8 | Heterogeneous Multiscale Methods: A Review显示文摘This paper gives a systematic introduction to HMM,the heterogeneous multiscale methods,including the fundamental design principles behind the HMM philosophy and the main obstacles that have to be overcome when using HMM for a particular problem.This is illustrated by examples from several application areas,including complex fluids,micro-fluidics,solids,interface problems,stochastic problems,and statistically self-similar problems.Emphasis is given to the technical tools,such as the various constrained molecular dynamics,that have been developed,in order to apply HMM to these problems.Examples of mathematical results on the error analysis of HMM are presented.The review ends with a discussion on some of the problems that have to be solved in order to make HMM a more powerful tool. | Weinan E Bjorn Engquist Xiantao Li Weiqing Ren Eric Vanden-Eijnden | 2007 | Communications in Computational Physics2007，2，3： | 4 |
| 9 | Outcomes of Medicare beneficiaries hospitalised with transient ischaemic attack and stratification using the ABCD^(2) score显示文摘Background Long-term outcomes for Medicare beneficiaries hospitalised with transient ischaemic attack(TIA)and role of ABCD^(2) score in identifying high-risk individuals are not studied.Methods We identified 40825 Medicare beneficiaries hospitalised from 2011 to 2014 for a TIA to a Get With The Guidelines(GWTG)-Stroke hospital and classified them using ABCD^(2)s of mortality and rehospitalisation(all-cause,ischaemic stroke,haemorrhagic stroke,myocardial infarction,and gastrointestinal and intracranial haemorrhage)for high-risk versus low-risk groups adjusted for patient and hospital characteristics.Results Of the 40825 patients,35118(86%)were high risk(ABCD^(2)≥4)and 5707(14%)were low risk(ABCD^(2)=0-3).Overall rate of mortality during 1-year follow-up after hospital discharge for the index TIA was 11.7%,44.3% were rehospitalised for any reason and 3.6%were readmitted due to stroke.Patients with ABCD^(2) score≥4 had higher mortality at 1 year than not(adjusted HR 1.18,95%CI 1.07 to 1.30).Adjusted risks for ischaemic stroke,all-cause readmission and mortality/all-cause readmission at 1 year were also significantly higher for patients with ABCD^(2) score≥4 vs 0-3.In contrast,haemorrhagic stroke,myocardial infarction,gastrointestinal bleeding and intracranial haemorrhage risk were not significantly different by ABCD^(2) score.Conclusions This study validates the use of ABCD^(2) score for long-term risk assessment after TIA in patients aged 65 years and older.Attentive efforts for community-based follow-up care after TIA are needed for ongoing prevention in Medicare beneficiaries who were hospitalised for TIA. | Shreyansh Shah Li Liang Durgesh Bhandary Saga Johansson Eric E Smith Deepak L Bhatt Gregg C Fonarow Naeem D Khan Eric Peterson Janet Prvu Bettger | 2021 | Stroke & Vascular Neurology2021，6，2： | 3 |
| 10 | Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial显示文摘 | Kris V Kowdley Eric Lawitz Israel Crespo Tarek Hassanein Mitchell N Davis Michael DeMicco David E Bernstein Nezam Afdhal John M Vierling Stuart C Gordon Jane K Anderson Robert H Hyland Hadas Dvory-Sobol Di An Robert G Hindes Efsevia Albanis William T Symo | 2013 | The Lancet2013，，9883： | 3 |
| 11 | A high-density, multi-parental SNP genetic map on apple validates a new mapping approach for outcrossing species显示文摘Quantitative trait loci(QTL)mapping approaches rely on the correct ordering of molecular markers along the chromosomes,which can be obtained from genetic linkage maps or a reference genome sequence.For apple(Malus domestica Borkh),the genome sequence v1 and v2 could not meet this need;therefore,a novel approach was devised to develop a dense genetic linkage map,providing the most reliable marker-loci order for the highest possible number of markers.The approach was based on four strategies:(i)the use of multiple full-sib families,(ii)the reduction of missing information through the use of HaploBlocks and alternative calling procedures for single-nucleotide polymorphism(SNP)markers,(iii)the construction of a single backcross-type data set including all families,and(iv)a two-step map generation procedure based on the sequential inclusion of markers.The map comprises 15417 SNP markers,clustered in 3 K HaploBlock markers spanning 1267 cM,with an average distance between adjacent markers of 0.37 cM and a maximum distance of 3.29 cM.Moreover,chromosome 5 was oriented according to its homoeologous chromosome 10.This map was useful to improve the apple genome sequence,design the Axiom Apple 480 K SNP array and perform multifamily-based QTL studies.Its collinearity with the genome sequences v1 and v3 are reported.To our knowledge,this is the shortest published SNP map in apple,while including the largest number of markers,families and individuals.This result validates our methodology,proving its value for the construction of integrated linkage maps for any outbreeding species. | Erica A Di Pierro Luca Gianfranceschi Mario Di Guardo Herma JJ Koehorst-van Putten Johannes W Kruisselbrink Sara Longhi Michela Troggio Luca Bianco Hélène Muranty Giulia Pagliarani Stefano Tartarini Thomas Letschka Lidia Lozano Luis Larisa Garkava-Gustavsson Diego Micheletti Marco CAM Bink Roeland E Voorrips Ebrahimi Aziz Riccardo Velasco François Laurens W Eric van de Weg | 2016 | Horticulture Research2016，3，1： | 3 |
| 12 | Sclerostin activity plays a key role in the negative effect of glucocorticoid signaling on osteoblast function in mice显示文摘Stress during prenatal development is correlated with detrimental cognitive and behavioral outcomes in offspring. However, the long-term impact of prenatal stress(PS) and disrupted glucocorticoid signaling on bone mass and strength is not understood. In contrast, the detrimental effect of lead(Pb) on skeletal health is well documented. As stress and Pb act on common biological targets via glucocorticoid signaling pathways and co-occur in the environment, this study first sought to assess the combined effect of stress and Pb on bone quality in association with alterations in glucocorticoid signaling. Bone parameters were evaluated using microCT, histomorphometry, and strength determination in 8-month-old male mouse offspring subjected to PS on gestational days 16 and 17, lifetime Pb exposure(100 p.p.m. Pb in drinking water), or to both. Pb reduced trabecular bone mass and, when combined with PS, Pb unmasked an exaggerated decrement in bone mass and tensile strength. Next, to characterize a mechanism of glucocorticoid effect on bone, prednisolone was implanted subcutaneously(controlled-release pellet, 5 mg·kg^(-1) per day) in 5-month-old mice that decreased osteoblastic activity and increased sclerostin and leptin levels. Furthermore, the synthetic glucocorticoid dexamethasone alters the anabolic Wnt signaling pathway. The Wnt pathway inhibitor sclerostin has several glucocorticoid response elements, and dexamethasone administration to osteoblastic cells induces sclerostin expression. Dexamethasone treatment of isolated bone marrow cells decreased bone nodule formation, whereas removal of sclerostin protected against this decrement in mineralization.Collectively, these findings suggest that bone loss associated with steroid-induced osteoporosis is a consequence of sclerostin-mediated restriction of Wnt signaling, which may mechanistically facilitate glucocorticoid toxicity in bone. | Eric E Beier Tzong-Jen Sheu Emily A Resseguie Masahiko Takahata Hani A Awad Deborah A Cory-Slechta J Edward Puzas | 2017 | Bone Research2017，5，2： | 3 |
| 13 | Combination drug regimens for metastatic clear cell renal cell carcinoma显示文摘Renal cell carcinomas(RCC)make up about 90%of kidney cancers,of which 80%are of the clear cell subtype.About 20%of patients are already metastatic at the time of diagnosis.Initial treatment is often cytoreductive nephrectomy,but systemic therapy is required for advanced RCC.Single agent targeted therapies are moderately toxic and only somewhat effective,leading to development of immunotherapies and combination therapies.This review identifies limitations of monotherapies for metastatic renal cell carcinoma,discusses recent advances in combination therapies,and highlights therapeutic options under development.The goal behind combining various modalities of systemic therapy is to potentiate a synergistic antitumor effect.However,combining targeted therapies may cause increased toxicity.The initial attempts to create therapeutic combinations based on inhibition of the vascular endothelial growth factor or mammalian target of rapamycin pathways were largely unsuccessful in achieving a profile of increased synergy without increased toxicity.To date,five combination therapies have been approved by the U.S.Food and Drug Administration,with the most recently approved therapies being a combination of checkpoint inhibition plus targeted therapy.Several other combination therapies are under development,including some in the phase 3 stage.The new wave of combination therapies for metastatic RCC has the potential to increase response rates and improve survival outcomes while maintaining tolerable side effect profiles. | Viraj V Khetani Daniella E Portal Mansi R Shah Tina Mayer Eric A Singer | 2020 | World Journal of Clinical Oncology2020，11，8： | 2 |
| 14 | Performance characteristics of retrograde single-balloon endoscopy: A single center experience显示文摘AIM: To evaluate the technical success, diagnostic yield(DY) and therapeutic potential of retrograde single balloon enteroscopy(rS BE). METHODS: A retrospective review of 136 rS BE procedures performed at a tertiary academic referral center from January 2006 and September 2013 was completed. Patient characteristics including age, gender and inpatient status were collected. The indication for the procedure was categorized into one of three groups: Obscure gastrointestinal bleeding(GIB), evaluation for Crohn's disease and abnormal imaging. Procedural characteristics including insertion depth(ID), procedure time, concordance with pre-procedural imaging and complications were also recorded. Lastly, DY, defined as the percentage of cases producing either a definitive diagnosis or findings that could explain clinical symptoms and therapeutic yield(TY), defined as the percentage of cases in which a definitive intervention was performed, were determined. Mucosal tattooing and biopsy alone were not included in the TY. RESULTS: A total of 136 rS BE procedures were identified. Mean patient age was 57.5(± 16.2) years, 67(49.2%) were male, and 110(80.9%) procedures were performed on an outpatient basis. Indications for rS BE included GIB in 55(40.4%), evaluation of inflammatory bowel disease(IBD) in 29(21.3%), and imaging suggestive of pathology other than GIB or IBD in 43(31.6%). Nine(6.6%) rS BEs were performed for other indications. Mean ID was 68.3(± 39.3) cm proximal to the ileocecal valve and mean time to completion was 41.7(± 15.5) min. Overall, 73(53.7%) cases were diagnostic and 25(18.4%) cases were therapeutic in which interventions(argon plasma coagulation, stricture dilatation, polypectomy, etc.) were performed. Pre-procedural imaging was performed in 88(64.7%) patients. Endoscopic concordance of positive imaging findings was seen in 31(35.2%) cases. Follow up data was available in 93(68.4%) patients; 2(2.2%) reported post-procedural abdominal pain within 30 d following rS BE. There were no other reported complications. CONCLUSION: rS BE exhibits an acceptable diagnostic and TY, rendering it a safe and effective procedure for the evaluation and treatment of small bowel diseases. | Kaci E Christian Karan Kapoor Eric M Goldberg | 2016 | World Journal of Gastrointestinal Endoscopy2016，8，15： | 2 |
| 15 | Neurocognitive Performance in Hypertensive Patients after Spine Surgery显示文摘 | Gene T. Yocum John G. Gaudet Lauren A. Teverbaugh Donald O. Quest Paul C. McCormick E Sander Connolly Eric J. Heyer | 2009 | Anesthesiology2009，，2： | 2 |
| 16 | Bayesian Analysis of Stochastic Volatility Models显示文摘 | Eric Jacquier Nicholas G Polson Peter E Rossi | 2002 | Journal of Business & Economic Statistics2002，，1： | 2 |
| 17 | Acute sensorineural hearing loss associated with peginterferon and ribavirin combination therapy during hepatitis C treatment: Outcome after resumption of therapy显示文摘Peginterferon and ribavirin combination therapy for the treatment of hepatitis C virus (HCV) is well known to be associated with significant adverse effects. Sensorineural hearing loss, that in most cases is unilateral, has been reported as a consequence of therapy with both non-pegylated and pegylated interferon (pegIFN) but is not a well-known adverse effect. We report a 45-year-old Caucasian woman who developed acute sensorineural hearing loss 2 mo after starting therapy with pegIFN-α 2b and ribavirin for the treatment of chronic HCV, genotype 1a. She did not report the hearing loss to the hepatitis clinic until L mo,later whereupon therapy was promptly discontinued.Although her serum alanine aminotransferase (ALT)normalized and her HCV-RNA became undetectable after 12 wk of pegIFN and ribavirin therapy, after discontinuation,her HCV-RNA became detectable with significant elevations of serum ALT. Four months after initial discontinuation,the patient re-commenced pegIFN and ribavirin combination therapy. After 44 of 48 wk of therapy, the patient's liver biochemistry has normalized and the HCV-RNA is undetectable. She has not developed worsening of her hearing loss and hearing on the left-side is unaffected.Both patients and physicians should be aware that sensorineural hearing loss may occur with pegIFN therapy.Our experience suggests that re-institution of therapy is not always associated with further hearing impairment. | Victor K Wong Cindy Cheong-Lee Jo-Ann E Ford Eric M Yoshida | 2005 | World Journal of Gastroenterology2005，11，34： | 2 |
| 18 | Role of Small Bowel Follow-through in Diagnosing Inflammation of the Terminal Ileum in Pediatric Patients显示文摘 | Matthew Stenerson Eric Vittinghoff Melvin B Heyman Grace E Kim Neera Gupta | 2010 | Journal of Pediatric Gastroenterology and Nutrition2010，，4： | 2 |
| 19 | Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration显示文摘 | Joanna M Wardlaw Eric E Smith Geert J Biessels Charlotte Cordonnier Franz Fazekas Richard Frayne Richard I Lindley John T O’Brien Frederik Barkhof Oscar R Benavente Sandra E Black Carol Brayne Monique Breteler Hugues Chabriat Charles DeCarli Frank-Erik de | 2013 | Lancet Neurology2013，，8： | 2 |
| 20 | Enhanced caveolin-1 expression in smooth muscle cells: Possible prelude to neointima formation显示文摘AIM: To study the genesis of neointima formation in pulmonary hypertension(PH), we investigated the role of caveolin-1 and related proteins. METHODS: Male Sprague Dawley rats were given monocrotaline(M, 40 mg/kg) or subjected to hypobaric hypoxia(H) to induce PH. Another group was given M and subjected to H to accelerate the disease process(M + H). Right ventricular systolic pressure, right ventricular hypertrophy, lung histology for medial hypertrophy and the presence of neointimal lesions were examined at 2 and 4 wk. The expression of caveolin-1 and its regulatory protein peroxisome proliferator-activated receptor(PPAR) γ, caveolin-2, proliferative and antiapoptotic factors(PY-STAT3, p-Erk, Bcl-x L), endothelial nitric oxide synthase(e NOS) and heat shock protein(HSP) 90 in the lungs were analyzed, and the results from M + H group were compared with the controls, M and H groups. Double immunofluorescence technique was used to identify the localization of caveolin-1 in pulmonary arteries in rat lungs and in human PH lung tissue. RESULTS: In the M + H group, PH was more severe compared with M or H group. In the 4 wk M+H group, several arteries with reduced caveolin-1 expression in endothelial layer coupled with an increased expression in smooth muscle cells(SMC), exhibited neointimal lesions. Neointima was present only in the arteries exhibiting enhanced caveolin-1 expression in SMC. Lung tissue obtained from patients with PH also revealed neointimal lesions only in the arteries exhibiting endothelial caveolin-1 loss accompanied by an increased caveolin-1 expression in SMC. Reduction in e NOS and HSP90 expression was present in the M groups(2 and 4 wk), but not in the M + H groups. In both M groups and in the M + H group at 2 wk, endothelial caveolin-1 loss was accompanied by an increase in PPARγ expression. In the M + H group at 4 wk, increase in caveolin-1 expression was accompanied by a reduction in the PPARγ expression. In the H group, there was neither a loss of endothelial caveolin-1, eNOS or HSP 90, nor an increase in SMC caveolin-1 expression; or any alteration in PPARγ expression. Proliferative pathways were activated in all experimental groups. CONCLUSION: Enhanced caveolin-1 expression in SMC follows extensive endothelial caveolin-1 loss with subsequent neointima formation. Increased caveolin-1 expression in SMC, thus, may be a prelude to neointima formation. | Jing Huang John H Wolk Michael H Gewitz James E Loyd James West Eric D Austin Rajamma Mathew | 2015 | World Journal of Cardiology2015，7，10： | 2 |
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