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1.
Background
Nitric oxide (NO) plays an important role in mobilization of endothelial progenitor cells (EPCs). We hypothesized that inhaled NO (iNO) would induce EPC mobilization and therefore promote lung repair in acute respiratory distress syndrome (ARDS).Methodology/Principal Findings
Healthy piglets were randomized into four groups (n = 6): Control (Con; mechanical ventilation only); ARDS (established by oleic acid infusion and mechanical ventilation); ARDS plus granulocyte-colony stimulating factor (G-CSF; 10 µg/kg/d subcutaneously); ARDS plus NO inhalation (iNO; 10 ppm). EPCs and mobilizing cytokines were assayed at different time points (baseline, 0, 24, 72 and 168 h) and injury reparation was assessed at 168 h. Compared to the Con group, the levels of EPCs were increased in bone marrow but not in blood in the ARDS group at 24 h. Compared to the ARDS group, inhaled NO induced a rapid elevation in the number of CD34+KDR+, KDR+CD133+ and CD34+KDR+CD133+ EPCs in blood (2163±454 vs. 1094±416, 1302±413 vs. 429±244, 1140±494 vs. 453±273 cells/ml, respectively, P<0.05), and a reduction in the percentage of KDR+CD133+ cells in bone marrow. Lung CD34, CD133, VEGF, VEGF receptor 2, endothelial NO synthase mRNA, and VEGF and VEGF receptor 2 protein expression levels were augmented in the iNO group, but not in the G-CSF group, compared to ARDS. Furthermore, iNO treatment reduced vascular permeability, increased pulmonary vessel density, and alleviated pulmonary edema and inflammation compared to ARDS treatment. Plasma VEGF, stromal cell-derived factor-1 (SDF-1) and bone marrow NO2 −/NO3 − were significantly higher in the iNO group compared to the ARDS group at 72 h.Conclusions
These results suggest that iNO induces mobilization of EPCs from bone marrow into circulation, contributes to vascular repair, and thereby alleviates lung damage. 相似文献2.
Francesco Tecilazich Thanh Dinh Leena Pradhan-Nabzdyk Ermelindo Leal Ana Tellechea Antonios Kafanas Charalambos Gnardellis Mary L. Magargee Andre Dejam Vasilis Toxavidis John C. Tigges Eugenia Carvalho Thomas E. Lyons Aristidis Veves 《PloS one》2013,8(12)
Background
To evaluate changes in endothelial progenitor cells (EPCs) and cytokines in patients with diabetic foot ulceration (DFU) in association with wound healing.Methods
We studied healthy subjects, diabetic patients not at risk of DFU, at risk of DFU and with active DFU. We prospectively followed the DFU patients over a 12-week period. We also investigated similar changes in diabetic rabbit and mouse models of wound healing.Results
All EPC phenotypes except the kinase insert domain receptor (KDR)+CD133+ were reduced in the at risk and the DFU groups compared to the controls. There were no major EPC differences between the control and not at risk group, and between the at risk and DFU groups. Serum stromal-cell derived factor-1 (SDF-1) and stem cell factor (SCF) were increased in DFU patients. DFU patients who healed their ulcers had lower CD34+KDR+ count at visits 3 and 4, serum c-reactive protein (CRP) and granulocyte-macrophage colony-stimulating factor (GM-CSF) at visit 1, interleukin-1 (IL-1) at visits 1 and 4. EPCs tended to be higher in both diabetic animal models when compared to their non-diabetic counterparts both before and ten days after wounding.Conclusions
Uncomplicated diabetes does not affect EPCs. EPCs are reduced in patients at risk or with DFU while complete wound healing is associated with CD34+KDR+ reduction, suggesting possible increased homing. Low baseline CRP, IL-1α and GM-CSF serum levels were associated with complete wound healing and may potentially serve as prognostic markers of DFU healing. No animal model alone is representative of the human condition, indicating the need for multiple experimental models. 相似文献3.
Sang-Mo Kwon Jun-Hee Lee Sang-Hun Lee Seok-Yun Jung Da-Yeon Kim Song-Hwa Kang So-Young Yoo Jong-Kyu Hong Ji-Hye Park Jung-Hee Kim Sung-Wook Kim Yeon-Ju Kim Sun-Jin Lee Hwi-Gon Kim Takayuki Asahara 《PloS one》2014,9(8)
Introduction
Despite the crucial role of endothelial progenitor cells (EPCs) in vascular regeneration, the specific interactions between EPCs and hematopoietic cells remain unclear.Methods
In EPC colony forming assays, we first demonstrated that the formation of EPC colonies was drastically increased in the coculture of CD34+ and CD34− cells, and determined the optimal concentrations of CD34+ cells and CD34− cells for spindle-shaped EPC differentiation.Results
Functionally, the coculture of CD34+ and CD34− cells resulted in a significant enhancement of adhesion, tube formation, and migration capacity compared with culture of CD34+ cells alone. Furthermore, blood flow recovery and capillary formation were remarkably increased by the coculture of CD34+ and CD34− cells in a murine hind-limb ischemia model. To elucidate further the role of hematopoietic cells in EPC differentiation, we isolated different populations of hematopoietic cells. T lymphocytes (CD3+) markedly accelerated the early EPC status of CD34+ cells, while macrophages (CD11b+) or megakaryocytes (CD41+) specifically promoted large EPC colonies.Conclusion
Our results suggest that specific populations of hematopoietic cells play a role in the EPC differentiation of CD34+ cells, a finding that may aid in the development of a novel cell therapy strategy to overcome the quantitative and qualitative limitations of EPC therapy. 相似文献4.
Objectives
Nonalcoholic fatty liver disease (NAFLD) is associated with advanced atherosclerosis and a higher risk of cardiovascular disease. Increasing evidence suggests that injured endothelial monolayer is regenerated by circulating bone marrow derived-endothelial progenitor cells (EPCs), and levels of circulating EPCs reflect vascular repair capacity. However, the relation between NAFLD and EPC remains unclear. Here, we tested the hypothesis that patients with nonalcoholic fatty liver disease (NAFLD) might have decreased endothelial progenitor cell (EPC) levels and attenuated EPC function.Methods and Results
A total of 312 consecutive patients undergoing elective coronary angiography because of suspected coronary artery disease were screened and received examinations of abdominal ultrasonography between July 2009 and November 2010. Finally, 34 patients with an ultrasonographic diagnosis of NAFLD, and 68 age- and sex-matched controls without NAFLD were enrolled. Flow cytometry with quantification of EPC markers (defined as CD34+, CD34+KDR+, and CD34+KDR+CD133+) in peripheral blood samples was used to assess circulating EPC numbers. The adhesive function, and migration, and tube formation capacities of EPCs were also determined in NAFLD patients and controls. Patients with NAFLD had a significantly higher incidence of metabolic syndrome, previous myocardial infarction, hyperuricemia, and higher waist circumference, body mass index, fasting glucose and triglyceride levels. In addition, patients with NAFLD had significantly decreased circulating EPC levels (all P<0.05), attenuated EPC functions, and enhanced systemic inflammation compared to controls. Multivariate logistic regression analysis showed that circulating EPC level (CD34+KDR+ [cells/105 events]) was an independent reverse predictor of NAFLD (Odds ratio: 0.78; 95% confidence interval: 0.69–0.89, P<0.001).Conclusions
NAFLD patients have decreased circulating EPC numbers and functions than those without NAFLD, which may be one of the mechanisms to explain atherosclerotic disease progression and enhanced cardiovascular risk in patients with NAFLD. 相似文献5.
Background
Inhaled nitric oxide (iNO) reduces death or need for extracorporeal membrane oxygenation (ECMO) in infants with persistent pulmonary hypertension of the newborn (PPHN). However, the response to iNO is variable and only 50–60% of infants demonstrate a response to iNO. It is not known why only some infants respond to iNO. Adults and children with blood groups B or AB do not respond as well to iNO as those with blood groups O/A.Methods/Principal Findings
To determine if blood group was associated with iNO response in newborn infants, a retrospective medical record review was done of infants admitted to a regional NICU from 2002-9 with a diagnosis of PPHN. Data were collected during the first twelve hours post-initiation of treatment. Of 86 infants diagnosed with PPHN, 23 infants had blood group A [18 received iNO], 21 had group B [18 with iNO], 40 had group O [36 with iNO], and 2 had group AB [both received iNO]. Change in PaO2/FiO2 was less in infants with blood group A, of whom less than half were responders (ΔPaO2/FiO2>20%) at 12 h versus 90% of infants with either O or B. Race, sex, birth weight, gestational age, Apgar scores at 1 and 5 minutes, and baseline PaO2/FiO2 were similar among groups. Outcomes including need for ECMO, death, length of ventilatory support, length of iNO use, and hospital stay were statistically not different by blood groups.Conclusions/Significance
Our results indicate that blood group influences iNO response in neonates. We hypothesize that either there is genetic linkage of the ABO gene locus with vasoregulatory genes, or that blood group antigens directly affect vascular reactivity. 相似文献6.
Background
Bone marrow-derived endothelial progenitor cells (EPCs), especially late EPCs, play a critical role in endothelial maintenance and repair, and postnatal vasculogenesis. Although the actin cytoskeleton has been considered as a modulator that controls the function and modulation of stem cells, its role in the function of EPCs, and in particular late EPCs, remains poorly understood.Methodology/Principal Finding
Bone marrow-derived late EPCs were treated with jasplakinolide, a compound that stabilizes actin filaments. Cell apoptosis, proliferation, adhesion, migration, tube formation, nitric oxide (NO) production and endothelial NO synthase (eNOS) phosphorylation were subsequently assayed in vitro. Moreover, EPCs were locally infused into freshly balloon-injured carotid arteries, and the reendothelialization capacity was evaluated after 14 days. Jasplakinolide affected the actin distribution of late EPCs in a concentration and time dependent manner, and a moderate concentration of (100 nmol/l) jasplakinolide directly stabilized the actin filament of late EPCs. Actin stabilization by jasplakinolide enhanced the late EPC apoptosis induced by VEGF deprivation, and significantly impaired late EPC proliferation, adhesion, migration and tube formation. Furthermore, jasplakinolide attenuated the reendothelialization capacity of transplanted EPCs in the injured arterial segment in vivo. However, eNOS phosphorylation and NO production were increased in late EPCs treated with jasplakinolide. NO donor sodium nitroprusside (SNP) rescued the functional activities of jasplakinolide-stressed late EPCs while the endothelial NO synthase inhibitor L-NAME led to a further dysfunction induced by jasplakinolide in late EPCs.Conclusions/Significance
A moderate concentration of jasplakinolide results in an accumulation of actin filaments, enhancing the apoptosis induced by cytokine deprivation, and impairing the proliferation and function of late EPCs both in vitro and in vivo. NO donor reverses these impairments, suggesting the role of NO-related mechanisms in jasplakinolide-induced EPC downregulation. Actin cytoskeleton may thus play a pivotal role in regulating late EPC function. 相似文献7.
Jér?me Avouac Maeva Vallucci Vanessa Smith Patricia Senet Barbara Ruiz Alberto Sulli Carmen Pizzorni Camille Frances Gilles Chiocchia Maurizio Cutolo Yannick Allanore 《Arthritis research & therapy》2013,15(2):R55
Introduction
We sought to assess whether nailfold videocapillaroscopy (NVC) patterns are associated with levels of angiogenic factors in systemic sclerosis (SSc).Methods
Circulating endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) were measured in the peripheral blood of 60 consecutive SSc patients. Serum levels of eight endothelial markers were measured first in these 60 patients, and then in an independent replication cohort of 43 SSc patients in case of association with NVC patterns. NVC patterns were determined by four independent investigators blinded to vascular markers.Results
Patients with the late-NVC pattern exhibited lower EPC levels (P < 0.0001) and higher VEGF levels (P = 0.03). Higher VEGF levels were confirmed to be associated with the late-NVC pattern in the replication cohort (P = 0.01). By multivariate analysis focused on biomarkers, lower EPC (P = 0.03) and higher VEGF levels (P = 0.001) were independently associated with the late-NVC pattern. In an alternate multivariate model including these two factors and SSc-related disease characteristics, lower EPC counts (P = 0.005), higher VEGF levels (P = 0.01), a history of digital ulcers (P = 0.04), and a modified Rodnan skin score > 14 (P < 0.0001) were independently associated with the late-NVC pattern.Conclusion
Our data revealed decreased EPC counts and increased VEGF levels in patients with the late-NVC pattern. Further studies are now needed to determine the role of VEGF and EPCs in endothelial injury and repair in SSc. 相似文献8.
Jonathan L. Slaughter Michael R. Stenger Patricia B. Reagan Sudarshan R. Jadcherla 《PloS one》2014,9(9)
Objective
To determine demographic and clinical variables associated with inhaled corticosteroid administration and to evaluate between-hospital variation in inhaled steroid use for infants with bronchopulmonary dysplasia (BPD).Design
Retrospective Cohort Study.Setting
Neonatal units of 35 US children''s hospitals; as recorded in the Pediatric Health Information System (PHIS) database.Patients
1429 infants with evolving BPD at 28 days who were born at <29 weeks gestation with birth weight <1500 grams, admitted within the first 7 postnatal days, and discharged between January 2007–June 2011.Results
Inhaled steroids were prescribed to 25% (n = 352) of the cohort with use steadily increasing during the first two months of hospitalization. The most frequently prescribed steroid was beclomethasone (n = 194, 14%), followed by budesonide (n = 125, 9%), and then fluticasone (n = 90, 6%). Birth gestation <24 weeks, birth weight 500–999 grams, and prolonged ventilation all increased the adjusted odds of ever receiving inhaled corticosteroids (p<0.05). Wide variations between hospitals in the frequency of infants ever receiving inhaled steroids (range: 0–60%) and the specific drug prescribed were noted. This variation persisted, even after controlling for observed confounders.Conclusions
Inhaled corticosteroid administration to infants with BPD is common in neonatal units within U.S. Children''s hospitals. However, its utilization varies markedly between centers from no treatment at some institutions to the majority of infants with BPD being treated at others. This supports the need for further research to identify the benefits and potential risks of inhaled steroid usage in infants with BPD. 相似文献9.
Martin Teraa Ralf W. Sprengers Peter E. Westerweel Hendrik Gremmels Marie-José T. H. Goumans Tom Teerlink Frans L. Moll Marianne C. Verhaar 《PloS one》2013,8(1)
Background
Critical limb ischemia (CLI) is characterized by lower extremity artery obstruction and a largely unexplained impaired ischemic neovascularization response. Bone marrow (BM) derived endothelial progenitor cells (EPC) contribute to neovascularization. We hypothesize that reduced levels and function of circulating progenitor cells and alterations in the BM contribute to impaired neovascularization in CLI.Methods
Levels of primitive (CD34+ and CD133+) progenitors and CD34+KDR+ EPC were analyzed using flow cytometry in blood and BM from 101 CLI patients in the JUVENTAS-trial () and healthy controls. Blood levels of markers for endothelial injury (sE-selectin, sICAM-1, sVCAM-1, and thrombomodulin), and progenitor cell mobilizing and inflammatory factors were assessed by conventional and multiplex ELISA. BM levels and activity of the EPC mobilizing protease MMP-9 were assessed by ELISA and zymography. Circulating angiogenic cells (CAC) were cultured and their paracrine function was assessed. NCT00371371Results
Endothelial injury markers were higher in CLI (P<0.01). CLI patients had higher levels of VEGF, SDF-1α, SCF, G-CSF (P<0.05) and of IL-6, IL-8 and IP-10 (P<0.05). Circulating EPC and BM CD34+ cells (P<0.05), lymphocytic expression of CXCR4 and CD26 in BM (P<0.05), and BM levels and activity of MMP-9 (P<0.01) were lower in CLI. Multivariate regression analysis showed an inverse association between IL-6 and BM CD34+ cell levels (P = 0.007). CAC from CLI patients had reduced paracrine function (P<0.0001).Conclusion
CLI patients have reduced levels of circulating EPC, despite profound endothelial injury and an EPC mobilizing response. Moreover, CLI patients have lower BM CD34+-cell levels, which were inversely associated with the inflammatory marker IL-6, and lower BM MMP-9 levels and activity. The results of this study suggest that inflammation-induced BM exhaustion and a disturbed progenitor cell mobilization response due to reduced levels and activity of MMP-9 in the BM and alterations in the SDF-1α/CXCR4 interaction contribute to the attenuated neovascularization in CLI patients. 相似文献10.
Chih-Hung Chen Li-Teh Chang Wei-Chih Tung Yung-Lung Chen Chia-Lo Chang Steve Leu Cheuk-Kwan Sun Tzu-Hsien Tsai I-Ting Tsai Hsueh-Wen Chang Hon-Kan Yip 《Journal of biomedical science》2012,19(1):66
Background
The roles of circulating endothelial progenitor cell (EPC) and mononuclear cell apoptosis (MCA) in liver cirrhosis (LC) patients are unknown. Moreover, vascular endothelial growth factor (VEGF) and stromal cell-derived factor (SDF)-1α are powerful endogenous substances enhancing EPC migration into circulation. We assessed the level and function of EPCs [CD31/CD34 (E1), KDR/CD34 (E2), CXCR4/CD34 (E3)], levels of MCA, VEGF and SDF-1α in circulation of LC patients.Methods
Blood sample was prospectively collected once for assessing EPC level and function, MCA, and plasma levels of VEGF and SDF-1α using flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively, in 78 LC patients and 25 age- and gender-matched healthy controls.Results
Number of EPCs (E1, E2, E3) was lower (all p < 0.0001), whereas SDF-1α level and MCA were higher (p < 0.001) in study patients compared with healthy controls. Number of EPCs (E2, E3) was higher but MCA was lower (all p < 0.05) in Child''s class A compared with Child''s class B and C patients, although no difference in VEGF and SDF-1α levels were noted among these patients. Chronic hepatitis B and esophageal varices bleeding were independently, whereas chronic hepatitis C, elevated aspartate aminotransferase (AST), and decompensated LC were inversely and independently correlated with circulating EPC level (all p < 0.03). Additionally, angiogenesis and transwell migratory ability of EPCs were reduced in LC patients than in controls (all p < 0.001).Conclusion
The results of this study demonstrated that level, angiogenic capacity, and function of circulating EPCs were significantly reduced, whereas plasma levels of SDF-1α and circulating MCA were substantially enhanced in cirrhotic patients. 相似文献11.
Background
Emerging evidence of histopathological analyses suggests that endothelial progenitor cells (EPCs) play an important role in vascular diseases. Neointimal hyperplasia can be reduced by intravenous transfusion of EPCs after vascular injury in mice. Therefore, it would be advantageous to develop an in vivo technique that can explore the temporal and spatial migration of EPCs homing to the damaged endothelium noninvasively.Methodology/Principal Findings
The left carotid common artery (LCCA) was injured by removal of endothelium with a flexible wire in Kunming mice. EPCs were collected by in vitro culture of spleen-derived mouse mononuclear cells (MNCs). EPCs labeling was carried out in vitro using Fe2O3-poly-L-lysine (Fe2O3-PLL). In vivo serial MR imaging was performed to follow-up the injured artery at different time points after intravenous transfusion of EPCs. Vessel wall areas of injured artery were computed on T2WI. Larger MR signal voids of vessel wall on T2WI was revealed in all 6 mice of the labeled EPC transfusion group 15 days after LCCA injury, and it was found only in 1 mouse in the unlabeled EPC transfusion group (p = 0.015). Quantitative analyses of vessel wall areas on T2WI showed that the vessel wall areas of labeled EPC transfusion group were less than those of unlabeled EPC transfusion group and control group fifteen days after artery injury (p<0.05). Histopathological analyses confirmed accumulation and distribution of transfused EPCs at the injury site of LCCA.Conclusions/Significance
These data indicate that MR imaging might be used as an in vivo method for the tracking of EPCs homing to the endothelium injured artery. 相似文献12.
Chien-Yi Hsu Po-Hsun Huang Chia-Hung Chiang Hsin-Bang Leu Chin-Chou Huang Jaw-Wen Chen Shing-Jong Lin 《PloS one》2013,8(7)
Background
Recent research indicates hypertensive patients with microalbuminuria have decreased endothelial progenitor cells (EPCs) and increased levels of endothelial apoptotic microparticles (EMP). However, whether these changes are related to a subsequent decline in glomerular filtration rate (GFR) remains unclear.Methods and Results
We enrolled totally 100 hypertensive out-patients with eGFR ≥30 mL/min/1.73 m2. The mean annual rate of GFR decline (△GFR/y) was −1.49±3.26 mL/min/1.73 m2 per year during the follow-up period (34±6 months). Flow cytometry was used to assess circulating EPC (CD34+/KDR+) and EMP levels (CD31+/annexin V+) in peripheral blood. The △GFR/y was correlated with the EMP to EPC ratio (r = −0.465, p<0.001), microalbuminuria (r = −0.329, p = 0.001), and the Framingham risk score (r = −0.245, p = 0.013). When we divided the patients into 4 groups according to the EMP to EPC ratio, there was an association between the EMP to EPC ratio and the ΔGFR/y (mean ΔGFR/y: 0.08±3.04 vs. −0.50±2.84 vs. −1.25±2.49 vs. −4.42±2.82, p<0.001). Multivariate analysis indicated that increased EMP to EPC ratio is an independent predictor of ΔeGFR/y.Conclusions
An increased circulating EMP to EPC ratio is associated with subsequent decline in GFR in hypertensive patients, which suggests endothelial damage with reduced vascular repair capacity may contribute to further deterioration of renal function in patients with hypertension. 相似文献13.
Background
There is increasing evidence that phloroglucinol, a compound from Ecklonia cava, induces the apoptosis of cancer cells, eventually suppressing tumor angiogenesis.Methodology/Principal Findings
This is the first report on phloroglucinol''s ability to potentially inhibit the functional bioactivities of endothelial progenitor cells (EPCs) and thereby attenuate tumor growth and angiogenesis in the Lewis lung carcinoma (LLC)-tumor-bearing mouse model. Although Phloroglucinol did not affect their cell toxicity, it specifically inhibited vascular endothelial growth factor (VEGF) dependent migration and capillary-like tube formation of EPCs. Our matrigel plug assay clearly indicated that orally injected phloroglucinol effectively disrupts VEGF-induced neovessel formation. Moreover, we demonstrated that when phloroglucinol is orally administered, it significantly inhibits tumor growth and angiogenesis as well as CD45−/CD34+ progenitor mobilization into peripheral blood in vivo in the LLC-tumor-bearing mouse model.Conclusions/Significance
These results suggest a novel role for phloroglucinol: Phloroglucinol might be a modulator of circulating EPC bioactivities, eventually suppressing tumorigenesis. Therefore, phloroglucinol might be a candidate compound for biosafe drugs that target tumor angiogenesis. 相似文献14.
Background
Despite strong evidence linking infections to the pathogenesis of bronchopulmonary dysplasia (BPD), limitations of bacterial culture methods have precluded systematic studies of airway organisms relative to disease outcomes. Application of molecular bacterial identification strategies may provide new insight into the role of bacterial acquisition in the airways of preterm infants at risk for BPD.Methods
Serial (within 72 hours, 7, 14, and 21 days of life) tracheal aspirate samples were collected from 10 preterm infants with gestational age ≤34 weeks at birth, and birth weight of 500–1250 g who required mechanical ventilation for at least 21 days. Samples were analyzed by quantitative real time PCR assays for total bacterial load and by pyrosequencing for bacterial identification.Results
Subjects were diagnosed with mild (1), moderate (3), or severe (5) BPD. One patient died prior to determination of disease severity. 107,487 sequences were analyzed, with mean of 3,359 (range 1,724–4,915) per sample. 2 of 10 samples collected <72 hours of life contained adequate bacterial DNA for successful sequence analysis, one of which was from a subject exposed to chorioamnionitis. All other samples exhibited bacterial loads >70copies/reaction. 72 organisms were observed in total. Seven organisms represented the dominant organism (>50% of total sequences) in 31/32 samples with positive sequences. A dominant organism represented>90% of total sequences in 13 samples. Staphylococcus, Ureaplasmaparvum, and Ureaplasmaurealyticum were the most frequently identified dominant organisms, but Pseudomonas, Enterococcus, and Escherichia were also identified.Conclusions
Early bacterial colonization with diverse species occursafter the first 3 days of life in the airways of intubated preterm infants, and can be characterized by bacterial load and marked species diversity. Molecular identification of bacteria in the lower airways of preterm infants has the potential to yield further insight into the pathogenesis of BPD. 相似文献15.
Chyong-Hsin Hsu Chia-Ying Lin Hsin Chi Jui-Hsing Chang Han-Yang Hung Hsin-An Kao Chun-Chih Peng Wai-Tim Jim 《PloS one》2014,9(10)
Objective
There is limited epidemiological data on the seasonality of respiratory syncytial virus (RSV) infection in subtropical climates, such as in Taiwan. This study aimed to assess RSV seasonality among children ≤24 months of age in Taiwan. We also assessed factors (gestational age [GA], chronologic age [CA], and bronchopulmonary dysplasia [BPD]) associated with RSV-associated hospitalization in preterm infants to confirm the appropriateness of the novel Taiwanese RSV prophylactic policy.Study Design
From January 2000 to August 2010, 3572 children aged ≤24-months were admitted to Taipei Mackay Memorial Hospital due to RSV infection. The monthly RSV-associated hospitalization rate among children aged ≤24 months was retrospectively reviewed. Among these children, 378 were born preterm. The associations between GA, CA, and BPD and the incidence of RSV-associated hospitalization in the preterm infants were assessed.Results
In children aged ≤24 months, the monthly distribution of RSV-associated hospitalization rates revealed a prolonged RSV season with a duration of 10 months. Infants with GAs ≤32 weeks and those who had BPD had the highest rates of RSV hospitalization (P<0.001). Preterm infants were most vulnerable to RSV infection within CA 9 months.Conclusions
Given that Taiwan has a prolonged (10-month) RSV season, the American Academy of Pediatrics'' recommendations for RSV prophylaxis are not directly applicable. The current Taiwanese guidelines for RSV prophylaxis, which specify palivizumab injection (a total six doses until CA 8–9 months) for preterm infants (those born before 286/7 weeks GA or before 356/7 weeks GA with BPD), are appropriate. This prophylaxis strategy may be applicable to other countries/regions with subtropical climates. 相似文献16.
Aim
The purpose of this project was to evaluate the influence of circulating endothelial progenitor cells (EPCs) and platelet microparticles (PMPs) on blood platelet function in experimental hypertension associated with hypercholesterolemia.Methods
Golden Syrian hamsters were divided in six groups: (i) control, C; (ii) hypertensive-hypercholesterolemic, HH; (iii) ‘prevention’, HHin-EPCs, HH animals fed a HH diet and treated with EPCs; (iv) ‘regression’, HHfin-EPCs, HH treated with EPCs after HH feeding; (v) HH treated with PMPs, HH-PMPs, and (vi) HH treated with EPCs and PMPs, HH-EPCs-PMPs.Results
Compared to HH group, the platelets from HHin-EPCs and HHfin-EPCs groups showed a reduction of: (i) activation, reflected by decreased integrin 3β, FAK, PI3K, src protein expression; (ii) secreted molecules as: SDF-1, MCP-1, RANTES, VEGF, PF4, PDGF and (iii) expression of pro-inflammatory molecules as: SDF-1, MCP-1, RANTES, IL-6, IL-1β; TFPI secretion was increased. Compared to HH group, platelets of HH-PMPs group showed increased activation, molecules release and proteins expression. Compared to HH-PMPs group the combination EPCs with PMPs treatment induced a decrease of all investigated platelet molecules, however not comparable with that recorded when EPC individual treatment was applied.Conclusion
EPCs have the ability to reduce platelet activation and to modulate their pro-inflammatory and anti-thrombogenic properties in hypertension associated with hypercholesterolemia. Although, PMPs have several beneficial effects in combination with EPCs, these did not improve the EPC effects. These findings reveal a new biological role of circulating EPCs in platelet function regulation, and may contribute to understand their cross talk, and the mechanisms of atherosclerosis. 相似文献17.
Min Cheng Xiumei Guan Hong Li Xiaodong Cui Xiaoyun Zhang Xin Li Xu Jing Haiyan Wu Emil Avsar 《PloS one》2013,8(7)
Background
Previous studies have demonstrated that endothelial progenitor cells (EPCs), in particular late EPCs, play important roles in endothelial maintenance and repair. Recent evidence has revealed shear stress as a key regulator for EPC differentiation. However, the underlying mechanisms regulating the shear stress–induced EPC differentiation have not been understood completely. The present study was undertaken to further investigate the effects of shear stress on the late EPC differentiation, and to elucidate the signal mechanism involved.Methodology/Principal Finding
In vitro and in vivo assays revealed that cytoskeletal remodeling was involved in the shear stress-upregulated expression of endothelial markers vWF and CD31 in late EPCs, with subsequently increased in vivo reendothelialization after arterial injury. Moreover, shear stress activated several mechanosensitive molecules including integrin β1, Ras, ERK1/2, paxillin and FAK, which were all involved in both cytoskeletal rearrangement and cell differentiation in response to shear stress in late EPCs.Conclusions/Significance
Shear stress is a key regulator for late EPC differentiation into endothelial cells, which is important for vascular repair, and the cytoskeletal rearrangement mediated by the activation of the cascade of integrin β1, Ras, ERK1/2, paxillin and FAK is crucial in this process. 相似文献18.
Schmidt-Lucke C Fichtlscherer S Aicher A Tschöpe C Schultheiss HP Zeiher AM Dimmeler S 《PloS one》2010,5(11):e13790
Aims
Circulating endothelial progenitor cells (EPC), involved in endothelial regeneration, neovascularisation, and determination of prognosis in cardiovascular disease can be characterised with functional assays or using immunofluorescence and flow cytometry. Combinations of markers, including CD34+KDR+ or CD133+KDR+, are used. This approach, however may not consider all characteristics of EPC. The lack of a standardised protocol with regards to reagents and gating strategies may account for the widespread inter-laboratory variations in quantification of EPC. We, therefore developed a novel protocol adapted from the standardised so-called ISHAGE protocol for enumeration of haematopoietic stem cells to enable comparison of clinical and laboratory data.Methods and Results
In 25 control subjects, 65 patients with coronary artery disease (CAD; 40 stable CAD, 25 acute coronary syndrome/acute myocardial infarction (ACS)), EPC were quantified using the following approach: Whole blood was incubated with CD45, KDR, and CD34. The ISHAGE sequential strategy was used, and finally, CD45dimCD34+ cells were quantified for KDR. A minimum of 100 CD34+ events were collected. For comparison, CD45+CD34+ and CD45−CD34+ were analysed simultaneously. The number of CD45dimCD34+KDR+ cells only were significantly higher in healthy controls compared to patients with CAD or ACS (p = 0.005 each, p<0.001 for trend). An inverse correlation of CD45dimCD34+KDR+ with disease activity (r = −0.475, p<0.001) was confirmed. Only CD45dimCD34+KDR+ correlated inversely with the number of diseased coronaries (r = −0.344; p<0.005). In a second study, a 4-week de-novo treatment of atorvastatin in stable CAD evoked an increase only of CD45dimCD34+KDR+ EPC (p<0.05). CD45+CD34+KDR+ and CD45−CD34+KDR+ were indifferent between the three groups.Conclusion
Our newly established protocol adopted from the standardised ISHAGE protocol achieved higher accuracy in EPC enumeration confirming previous findings with respect to the correlation of EPC with disease activity and the increase of EPC during statin therapy. The data of this study show the CD45dim fraction to harbour EPC. 相似文献19.
Background
Cilostazol(CLZ) has been used as a vasodilating anti-platelet drug clinically and demonstrated to inhibit proliferation of smooth muscle cells and effect on endothelial cells. However, the effect of CLZ on re-endothelialization including bone marrow (BM)-derived endothelial progenitor cell (EPC) contribution is unclear. We have investigated the hypothesis that CLZ might accelerate re-endothelialization with EPCs.Methodology/Principal Findings
Balloon carotid denudation was performed in male Sprague-Dawley rats. CLZ group was given CLZ mixed feed from 2weeks before carotid injury. Control group was fed normal diet. CLZ accelerated re-endothelialization at 2 weeks after surgery and resulted in a significant reduction of neointima formation 4 weeks after surgery compared with that in control group. CLZ also increased the number of circulating EPCs throughout the time course. We examined the contribution of BM-derived EPCs to re-endothelialization by BM transplantation from Tie2/lacZ mice to nude rats. The number of Tie2-regulated X-gal positive cells on injured arterial luminal surface was increased at 2 weeks after surgery in CLZ group compared with that in control group. In vitro, CLZ enhanced proliferation, adhesion and migration activity, and differentiation with mRNA upregulation of adhesion molecule integrin αvβ3, chemokine receptor CXCR4 and growth factor VEGF assessed by real-time RT-PCR in rat BM-derived cultured EPCs. In addition, CLZ markedly increased the expression of SDF-1α that is a ligand of CXCR4 receptor in EPCs, in the media following vascular injury.Conclusions/Significance
CLZ promotes EPC mobilization from BM and EPC recruitment to sites of arterial injury, and thereby inhibited neointima formation with acceleration of re-endothelialization with EPCs as well as pre-existing endothelial cells in a rat carotid balloon injury model. CLZ could be not only an anti-platelet agent but also a promising tool for endothelial regeneration, which is a key event for preventing atherosclerosis or restenosis after vascular intervention. 相似文献20.
Hibbert B Ma X Pourdjabbar A Simard T Rayner K Sun J Chen YX Filion L O'Brien ER 《PloS one》2011,6(1):e16413