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1.
Pan Zhang Jingwei Feng Yunjun Liao Junrong Cai Tao Zhou Mingliang Sun Jianhua Gao Kai Gao 《Biochemical and biophysical research communications》2018,495(3):2249-2256
Background
Flap necrosis due to insufficient blood supply is a common postoperative complication in random pattern flaps. Stem cell therapies have emerged as promising biologics for tissue ischemia. A novel fat derived product, stromal vascular fraction gel (SVF-gel), can be prepared with lipoaspirate through simple mechanical processing, removing only the lipid content. SVF-gel enriches adipose-derived stem cells and potentially beneficial for flap necrosis.Methods
Nude mice ischemic flaps were treated with human SVF-gel, stromal vascular fraction (SVF) cell suspension or saline (n = 10). They were injected to the flap recipient beds, and necrosis and vascularization was assessed on postoperative day 14. We harvested the necrosis-free distal to evaluated skin healthiness and neovasculogenesis by Masson's trichrome stain and immunofluorescence, etc. Pro-angiogenic factors were assessed with tissue qRT-PCR. Finally, we traced the grafted human tissue with immunofluorescence.Results
SVF-gel-treated flaps have the smallest necrotic zones (22.05% ± 0.0438) compared with the saline controls (53.78% ± 0.1412) or SVF-treated ones (35.54% ± 0.0850, p = 0.039). Numerous functional musculocutaneous perforators were developed around SVF-gel grafts. The SVF-gel-treated skin had the best fat restoration (231.3 ± 48.1 μm) among three groups (F = 10.83, p = 0.0102) while saline-treated flap distal appeared fibrotic. SVF-gel-treated flaps also had ～43% more CD31 + capillaries (p = 0.0152) with ～3 folds more gene expression of angiogenic cytokines of VEGF and bFGF (p = 0.0310 and 0.0303, respectively) than saline-treated controls. Furthermore, we found hSVF-gel cells (hGolgi+) had directly engrafted as vessel component (α-smooth muscle actin, α-SMA+) to the flap.Conclusion
Adipose cellular matrix enhanced flap neovascularization partly by direct incorporation, improved flap survival and fat restoration. The composition-selective fat grafting with SVF-gel demonstrated efficacy comparable with stem cell therapy and is especially valuable for clinical translation. 相似文献2.
Shuilian Luo Yuhang Chen Rui He Yujun Shi Li Su 《Biochemical and biophysical research communications》2018,495(1):607-613
Objective
The decreased expression of muscle-specific microRNA-1 (miR-1) has been found in many cardiovascular diseases and is considered to contribute to heart failure (HF). Here we investigated the role of miR-1 in myocardium protection by infusion of miR-1 in a cardiac global miRNA-deficient mouse.Methods
We generated a cardiac-selective miRNA-deficient mouse by crossing Dicerflox/flox mice with mice expressing tamoxifen-inducible Cre recombinase under the control of a mouse αMHC promoter. When Dicer gene was removed following tamoxifen injection, the mice were treated with micrONTM mmu-miR-1a-3p agomir (agomir-1). The mice were subjected to echocardiography measurement, and the heart tissue specimens were stained with hematoxylin and eosin (H&E) and Sirius red. Terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling assay and Ki67 immunofluorescence were used to determine apoptosis and proliferation.Results
Dicer deletion resulted in extensive decrease in cardiac miRNAs in the mice. In echocardiography, the mice developed rapid and dramatic left ventricular enlargement. In histology, apparent cardiomyocyte hypertrophy, myofiber disarray, ventricular fibrosis, inflammatory infiltration, and severe ventricular remodeling were exhibited. When the mice were treated with agomir-1, they did not show any significant abnormalities in heart structure and histology in response to Dicer ablation.Conclusion
The proper expression of miRNAs plays vital roles in the maintenance of heart histology and function. Among these miRNAs, miR-1 is critical to inhibit myocyte hypertrophy and extracellular matrix deposition, thereby preventing cardiac remodeling in cardiac-selective Dicer deficient mice. 相似文献3.
4.
Tomohiro Ueda Tomohisa Takagi Kazuhiro Katada Takaya Iida Katsura Mizushima Osamu Dohi Tetsuya Okayama Naohisa Yoshida Kazuhiro Kamada Kazuhiko Uchiyama Osamu Handa Takeshi Ishikawa Hideyuki Konishi Yuji Naito Yukio Nagasaki Yoshito Itoh 《Biochemical and biophysical research communications》2018,495(2):2044-2049
Background
Intestinal ischemia-reperfusion (I-R) injury is a serious abdominal condition leading to multiple organ failure with high mortality. However, no reliable treatment is available. A redox nanoparticle (RNPO) was recently developed, and its efficacy for several intestinal inflammatory conditions has been reported. To this end, the aim of this study was to investigate the therapeutic effects of RNPO on intestinal I-R injury in mice.Methods
Ischemia was induced in the small intestine of C57BL/6 mice by occluding the superior mesenteric artery for 45 min under anesthesia followed by reperfusion for 4 h. Mice were orally administered the vehicle or RNPO 1 h before ischemia. Inflammatory markers such as histological findings, thiobarbituric acid (TBA)-reactive substances as an index of lipid peroxidation, myeloperoxidase (MPO) activity as an index of neutrophil infiltration, and expression of pro-inflammatory cytokine mRNA in the intestinal mucosa were assessed.Results
Induction of I-R caused a significant increase in inflammatory markers (histological scores, TBA-reactive substances, MPO activity, and expression of keratinocyte chemoattractant mRNA). These changes were significantly attenuated in RNPO-treated mice as compared to vehicle-treated mice.Conclusion
Orally administered RNPO attenuated intestinal I-R injury in mice in association with reductions in neutrophil infiltration and lipid peroxidation, suggesting the possibly potential of RNPO as a therapeutic agent for intestinal I-R injury. 相似文献5.
Xu Gao Avirup Guha Benjamin Buck Dilesh Patel Melissa J. Snider Michael Boyd Muhammad Afzal Auroa Badin Hemant Godara Zhenguo Liu Jaret Tyler Raul Weiss Steven Kalbfleisch John Hummel Ralph Augostini Mahmoud Houmsse Emile G. Daoud 《Indian pacing and electrophysiology journal》2018,18(2):68-72
Background
Expert opinion recommends performing exercise testing with initiation of Class Ic antiarrhythmic medication.Objective
To evaluate the rate and reason for discontinuation of Ic agent within the first year of follow up, with particular attention to rate of proarrhythmia and the value of routine treadmill testing.Methods
This is a single center retrospective cohort study including consecutive patients with atrial arrhythmias who were initiated on a Class Ic agent from 2011 to 2016. Data was collated from chart review and pharmacy database.Results
The study population included 300 patients (55% male, mean age 61; mean ejection fraction, 56%) started on flecainide (n = 153; 51%) and propafenone (n = 147; 49%). Drug initiation was completed while hospitalized on telemetry and the staff electrophysiologists directed dosing. There was one proarrhythmic event during initiation (0.3%). The primary reason for not being discharged on Ic agent was due to detection of proarrhythmia (n = 15) or ischemia (n = 1) with treadmill testing (5.3%). Exercise testing was the single significant variable to affect the decision to discontinue Ic drug, p < 0.0001 (95% CI: 1.89–6.08%). During follow up, the primary reason for discontinuation of Ic agent was lack of efficacy, 32%.Conclusions
With proper screening, initiation of Class Ic agent is associated with very low rate of proarrhythmia. Treadmill testing is of incremental value and should be completed in all patients after loading Class Ic antiarrhythmic. 相似文献6.
7.
Amirfarjam Fazelifar Fatemeh Jorfi Majid Haghjoo 《Indian pacing and electrophysiology journal》2018,18(1):13-19
Background
With increasing use of cardiac resynchronization therapy (CRT), treating physicians should be familiar with different electrocardiographic (ECG) patterns of left ventricular (LV) lead and biventricular (BiV) pacing. However, there are a few publications on ECG patterns during BiV pacing.Purpose
This study was sought to determine different ECG patterns in patients with BiV pacing.Methods
Twelve-lead ECGs during BiV pacing (right ventricular leads at apex and LV leads in one of the lateral coronary veins) were analyzed in 181 consecutive patients (121 male; mean age, 62.0 ± 13.5 years) with advanced heart failure and baseline left bundle branch block pattern after at least 6-month of uncomplicated CRT.Results
During BiV pacing, 65% of the patients showed a dominant R wave in V1. There was a right axis deviation in 57% in frontal plane. However, a left superior axis emerged in 34% and normal frontal plane axis in 9%. Sequential BiV pacing (73% vs. 58%, P = 0.04) and pacing from posterolateral coronary vein (80% vs. 60%, p = 0.045) were more likely to present with a dominant R wave in V1. In sequential pacing, AV interval was significantly longer in patients with negative complex in V1 than in those with positive complex (124 ± 21 vs. 116 ± 8.0, p = 0.005). A Q/q wave was detected in 85% of patients in lead I and 78% in lead aVL.Conclusions
BiV pacing from lateral coronary venous branches and right ventricular apex characteristically presented with dominant R wave in V1, Q/q wave in leads I and aVL, and right or left superior axis. However, a negative complex in V1, QRS axis in other quadrants, and lack of Q/q wave in leads I and aVL did not necessarily indicate a problem. 相似文献8.
Akihiro Ito Tadashi Ishida Yasuyoshi Washio Akio Yamazaki Hiromasa Tachibana 《BMC pulmonary medicine》2017,17(1):211
Background
Because of a limited number of reports, we aimed to investigate the clinical characteristics of patients with Legionella pneumonia due to non-Legionella pneumophila serogroup 1 and the diagnostic usefulness of the six-point scoring system for such patients compared with patients with pneumonia caused by L. pneumophila serogroup 1.Methods
We retrospectively analysed patients diagnosed with Legionella pneumonia due to non-L. pneumophila serogroup 1 between March 2001 and June 2016. We examined the clinical characteristics, including symptoms, laboratory findings, radiologic findings, pneumonia severity, initial treatment and prognosis. We also calculated scores using the six-point scoring system in these patients. Furthermore, we compared the clinical characteristics and six-point scores between non-L. pneumophila serogroup 1 patients and L. pneumophila serogroup 1 patients among hospitalized community-acquired pneumonia patients enrolled prospectively between October 2010 and July 2016.Results
Eleven patients had pneumonia due to non-L. pneumophila serogroup 1; their median age was 66 years and 8 patients (72.7%) were male. The most common pathogen was L. pneumophila serogroup 3 (6/11), followed by L. pneumophila serogroup 9 (3/11), L. pneumophila serogroup 6 (1/11) and L. longbeachae (1/11). Non-specific symptoms, such as fever and cough, were common. Six patients (54.5%) had liver enzyme elevation, but no patient developed hyponatraemia at <130 mEq/L. Nine patients (81.8%) showed lobar pneumonia and 7 patients (63.6%) manifested with consolidation and ground-glass opacity. Patients with mild to moderate severity comprised 10 (90.9%) by CURB-65 and 5 (45.5%) by the Pneumonia Severity Index. Of all patients, 4 were admitted to the intensive care unit and 3 died despite appropriate empiric therapy. The clinical characteristics were not significantly different between non-L. pneumophila serogroup 1 patients and L. pneumophila serogroup 1 patients (n?=?23). At a cut-off value of ≥?2 points, the sensitivity of the six-point scoring system was 54.5% (6/11) for non-L. pneumophila serogroup 1 patients and 95.7% (22/23) for L. pneumophila serogroup 1 patients.Conclusions
Cases of non-L. pneumophila serogroup 1 pneumonia varied in severity from mild to severe and the clinical characteristics were often non-specific. The six-point scoring system was not useful in predicting such Legionella pneumonia cases.9.
Yingjie Wang Wei Zhu Ke Xiao Zeng Li Qi Ma Weifeng Li Songpo Shen Xisheng Weng 《Biochemical and biophysical research communications》2019,508(1):25-30
Background
HA modified by bisphosphonate (BP) (HA-BP) was synthesized by chemical reaction and possessed promising properties such as self-healing, injection ability, and strong adhesion. The main aim of this study was to confirm its role in promoting osteogenic differentiation in vitro and bone regeneration in vivo.Methods
The cell biocompatibility of this material was determined using the CCK-8 assay. Alkaline phosphatase (ALP), osteocalcin (OT), vascular endothelial growth factor (VEGF), and collagen I were assessed by quantitative real-time polymerase chain reaction (Q-PCR) in the treated group. The number and density of calcium nodules and ALP were evaluated by Alizarin Red staining and ALP staining. We have successfully developed an animal model simulating osteonecrosis of the femoral head (ONFH). Utilizing this animal model, the impact of HA-BP/CaP on bone formation was assessed. The amount of bone regeneration at 1 and 2 months after HA-BP/CaP injection was estimated by micro-computed tomography (micro-CT) analysis and H&E, collagen I, and periostin staining.Results
The number of cells gradually increased in the experimental group over time and was close to that of the blank control group. ALP, collagen I, and VEGF expression was significantly higher in the experimental group than in the blank group (VEGF, ALP, both **p < 0.01; collagen I, ***p<0.001). In addition, the number and density of calcium nodules and ALP was clearly greater in the material group than in the control group.The quantification analysis showed that the mineral contents of regenerated bone at 1 and 2 months after HA-BP/CaP injection were significantly greater than those in the control group, according to micro-CT evaluation (**p<0.01). The amount of organic components in the HA-BP/CaP group was greater than that in the control group after decalcification and H&E staining. In addition, collagen I and periostin staining further confirmed the results of H&E staining.Conclusion
This material can boost proliferation and osteogenic differentiation of MC3T3-E1 cells in vitro. It can intensely accelerate bone regeneration in vivo, which is a promising strategy for tissue engineering. 相似文献10.
Background
Legionella pneumophila, is an intracellular pathogen that causes Legionnaires'' disease in humans, a potentially lethal pneumonia. L. pneumophila has the ability to enter and replicate in the host and is essential for pathogenesis.Methodology/Principal Findings
Phagocytosis was measured by cell invasion assays. Construction of PI3K mutant by PCR cloning and expression of dominant negative mutant was detected by Western blot. PI3K activity was measured by 32P labeling and detection of phospholipids products by thin layer chromatography. Infection of macrophages with virulent L. pneumophila stimulated the formation of phosphatidylinositol 3-phosphate (PIP3), a phosphorylated lipid product of PI3K whereas two structurally distinct phosphatidylinositol 3 kinase (PI3K) inhibitors, wortmannin and LY294002, reduced L. pneumophila entry into macrophages in a dose-dependent fashion. Furthermore, PI3K activation led to Akt stimulation, a serine/threonine kinase, which was also inhibited by wortmannin and LY294002. In contrast, PI3K and protein kinase B (PKB/Akt) activities were lower in macrophages infected with an avirulent bacterial strain. Only virulent L. pneumophila increased lipid kinase activity present in immunoprecipitates of the p85α subunit of class I PI3K and tyrosine phosphorylated proteins. In addition, macrophages expressing a specific dominant negative mutant of PI3K reduced L. pneumophila entry into these cells.Conclusion/Significance
Entry of L. pneumophila is mediated by PI3K/Akt signaling pathway. These results suggest an important role for PI3K and Akt in the L. pneumophila infection process. They point to possible novel strategies for undermining L. pneumophila host uptake and reducing pathogenesis of Legionnaires'' disease. 相似文献11.
12.
Muhammad Umer Nisar Muhammad Bilal Munir Michael S. Sharbaugh Floyd W. Thoma Andrew D. Althouse Samir Saba 《Indian pacing and electrophysiology journal》2018,18(1):6-12
Aims
Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. Patients presenting with AF are often admitted to hospital for rhythm or rate control, symptom management, and/or anticoagulation. We investigated temporal trends in AF hospitalizations in United States from 1996 to 2010.Methods
Data were obtained from the National Hospital Discharge Survey (NHDS), a national probability sample survey of discharges conducted annually by National Center for Health Statistics. Because of the survey design, sampling weights were applied to the raw NHDS data to produce national estimates. Hospitalizations with a primary diagnosis of AF were identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code of 427.31. Weighted least squares regression was used to test for linear trends in the number of AF admissions, length of stay, and inpatient mortality. We further stratified AF admissions based on patients' age, gender, and race.Results
Admissions for a primary diagnosis of AF increased from approximately 286,000 in 1996 to about 410,000 in 2010 with a significant linear trend (β = 9470 additional admissions per year, p < 0.001). The trend of increased AF admissions was uniform across patient sub-groups. Overall, mean length of stay for AF admissions was 3.75 days, and this remained relatively stable over time (β = 0.002 days, p = 0.884). Inpatient mortality was 0.96% and also remained stable over time (β = 0.031%, p = 0.181).Conclusion
Our data demonstrate an increase in the number of AF admissions but constant length of stay and mortality over time. 相似文献13.
14.
Taichi Ikedo Manabu Minami Hiroharu Kataoka Kosuke Hayashi Manabu Nagata Risako Fujikawa Fumiyoshi Yamazaki Mitsutoshi Setou Masayuki Yokode Susumu Miyamoto 《Biochemical and biophysical research communications》2018,495(1):332-338
Object
The wall thickness of intracranial aneurysms (IAs) is heterogeneous. Although thinning of the IA wall is thought to contribute to IA rupture, the underlying mechanism remains poorly understood. Recently, imaging mass spectroscopy (IMS) has been used to reveal the distribution of phospholipids in vascular diseases. To investigate the feature of phospholipid composition of IA walls, we conducted IMS in a rat model of experimentally induced IA.Material and methods
IAs were surgically induced in 7-week-old male rats and analyzed by IMS in negative-ion mode.Results
A molecule at m/z 885.5 was more abundant in the thickened wall than in the thinned wall (P = 0.03). Multiple-stage mass spectroscopy revealed the molecule to be phosphatidylinositol containing stearic acid and arachidonic acid (PI 18:0/20:4). Immunohistochemistry indicated that vascular smooth muscle cells (SMCs) in the thickened wall had dedifferentiated phenotypes. To investigate the relationship between accumulation of PI (18:0/20:4) and phenotypic changes in SMCs, we subjected primary mouse aortic SMCs to liquid chromatography–tandem mass spectrometry. Notably, dedifferentiated SMCs had 1.3-fold more PI (18:0/20:4) than partly differentiated SMCs.Conclusions
Our study demonstrated the heterogeneity in phospholipid composition of the aneurysmal walls using experimentally induced IAs. PI (18:0/20:4) accumulated at high levels in the thickened aneurysmal wall where synthetic dedifferentiated SMCs exist, suggesting that this phospholipid may be involved in the phenotypic switching of medial SMCs in the IA wall. 相似文献15.
Objective
To elucidate the molecular mechanism of microRNA-215 (miR-215) in the migration and invasion of high grade glioma.Results
42 Patients were analysed for clinicopathological characteristics. qRT-PCR showed that miR-215 was up-regulated in glioma tissues compared with non-neoplastic brain tissues (P < 0.05). The up-regulated miR-215 was closely associated with high grade glioma (P < 0.01) and poor overall survival (P < 0.01). Transwell assay showed that re-expression of miR-215 enhanced migration and invasion of glioma cells. miR-215 also down-regulated retinoblastoma tumor suppressor gene 1 (RB1) expression by targeting its 3′-UTR. Reversely, re-expression of RB1 inhibited partial effect of miR-215 on migration and invasion in vitro.Conclusions
Re-expression of miR-215 promoted cell migration and invasion of glioma by targeting RB1. miR-215 can thus be used as a biomarker for tumor progression and prognosis in human high grade glioma.16.
U. Boles E.E. Gul L. Fitzgerald F. Sadiq Ali C. Nolan K. Aldworth-Gaumond D.R. Redfearn A. Baranchuk B. Glover C. Simpson H. Abdollah K.A. Michael 《Indian pacing and electrophysiology journal》2018,18(2):56-60
Background
Current algorithms and device morphology templates have been proposed in current Implantable Cardioverter-Defibrillators (ICDs) to minimize inappropriate therapies (ITS), but this has not been completely successful.Aim
Assess the impact of a deliberate strategy of using an atrial lead implant with standardized parameters; based on all current ICD discriminators and technologies, on the burden of ITS.Method
A retrospective single-centre analysis of 250 patients with either dual chamber (DR) ICDs or biventricular ICDs (CRTDs) over a (41.9 ± 27.3) month period was performed. The incidence of ITS on all ICD and CRTD patients was chronicled after the implementation of standardized programming.Results
39 events of anti-tachycardial pacing (ATP) and/or shocks were identified in 20 patients (8% incidence rate among patients). The total number of individual therapies was 120, of which 34% were inappropriate ATP, and 36% were inappropriate shocks. 11 patients of the 250 patients received ITS (4.4%). Of the 20 patients, four had ICDs for primary prevention and 16 for a secondary prevention. All the episodes in the primary indication group were inappropriate, while seven patients (43%) of the secondary indication group experienced inappropriate therapies.Conclusions
The burden of ITS in the population of patients receiving ICDs was 4.4% in the presence of atrial leads. The proposed rationalized programming criteria seems an effective strategy to minimize the burden of inappropriate therapies and will require further validation. 相似文献17.
Jem D. Lane Sarah Whittaker-Axon Richard J. Schilling Martin D. Lowe 《Indian pacing and electrophysiology journal》2019,19(2):49-54
Background
Implantable cardioverter-defibrillator (ICD) lead parameters may deteriorate due to right ventricular (RV) disease such as arrhythmogenic right ventricular cardiomyopathy (ARVC), with implications for safe delivery of therapies. We compared ICD and CRT-D (cardiac resynchronisation therapy-defibrillator) lead parameters in patients with ARVC and dilated cardiomyopathy (DCM).Methods
RV lead sensing (R wave amplitude) and pacing (threshold and amplitude-pulse width product (APWP)), left ventricular (LV) pacing (APWP), and imaging parameter trends were assessed in 18 patients with ARVC and 18 with DCM.Results
R wave amplitude did not change significantly over time in either group (over 5 years, ARVC -0.4 mV, 95% CI -3.8–3.0 mV; DCM -1.8 mV, 95% CI -5.0–1.3 mV). Within ARVC group, divergent trends were seen according to lead position. DCM patients experienced an increase in RV lead threshold (+1.1 V over 5 years, 95% CI + 0.5 to +1.7 V) and RV APWP (+0.48 Vms over 5 years, 95% CI + 0.24 to +0.71 Vms); ARVC patients had no change. ARVC patients had a higher LVEF at baseline than DCM patients (52 vs 20%, p < 0.001), though LVEF decreased over time for the former, while increasing for the latter. TAPSE did not change over time for ARVC patients.Conclusions
Lead parameters in ARVC patients were stable over medium-term follow up. In DCM patients, RV lead threshold and RV and LV APWP increased over time. These differential responses for DCM and ARVC were not explained by imaging indices, and may reflect distinct patterns of disease progression. 相似文献18.
Shilu Zhao Mingfang Li Weizhu Ju Lingyun Gu Fengxiang Zhang Hongwu Chen Kai Gu Bing Yang Minglong Chen 《Indian pacing and electrophysiology journal》2018,18(3):95-99
Background
Atrial tissue fibrosis can cause electrical or structural remodeling in patients with atrial fibrillation. Transforming growth factor beta 1(TGF-β1) signaling acts as a central role in fibroblast activation. In this report, we aimed to investigate the relationship between serum level of TGF-β1 and mean left atrial voltage in patients with chronic atrial fibrillation (CAF).Methods
A total of 16 consecutive adult patients with CAF who underwent catheter ablation were enrolled. Blood samples for measurement of TGF-β1 were collected from periphery veins and coronary sinus before pulmonary vein isolation. The measurement was performed with a commercially available ELISA kit. Cardiac indices were measured using echocardiography. The left atrial electroanatomic mapping was performed after pulmonary vein isolation.Results
Serum level of TGF-β1 in peripheral blood was higher than that in coronary sinus (p < 0.001). TGF-β1 serum level in coronary sinus negatively correlated with mean left atrial voltage (r = -0.650, p = 0.012), While periphery TGF-β1 level tended to be negatively correlated with mean left atrial voltage(r = -0.492, p = 0.053). Patients who treated with angiotensin II receptor antagonists had lower coronary sinus TGF-β1 serum level than those who did not treated with angiotensin II receptor antagonists (p = 0.046).Conclusion
Level of TGF-β1 in peripheral serum is higher than that in coronary sinus, and serum level of TGF-β1 in coronary sinus is negatively associated with mean left atrial voltage in patients with CAF, angiotensin II receptor antagonists could affect TGF-β1 serum level. 相似文献19.
Jamie L. Kuck Julie A. Bastarache Ciara M. Shaver Joshua P. Fessel Sergey I. Dikalov James M. May Lorraine B. Ware 《Biochemical and biophysical research communications》2018,495(1):433-437
Background
Increased endothelial permeability is central to shock and organ dysfunction in sepsis but therapeutics targeted to known mediators of increased endothelial permeability have been unsuccessful in patient studies. We previously reported that cell-free hemoglobin (CFH) is elevated in the majority of patients with sepsis and is associated with organ dysfunction, poor clinical outcomes and elevated markers of oxidant injury. Others have shown that Vitamin C (ascorbate) may have endothelial protective effects in sepsis. In this study, we tested the hypothesis that high levels of CFH, as seen in the circulation of patients with sepsis, disrupt endothelial barrier integrity.Methods
Human umbilical vein endothelial cells (HUVEC) were grown to confluence and treated with CFH with or without ascorbate. Monolayer permeability was measured by Electric Cell-substrate Impedance Sensing (ECIS) or transfer of 14C-inulin. Viability was measured by trypan blue exclusion. Intracellular ascorbate was measured by HPLC.Results
CFH increased permeability in a dose- and time-dependent manner with 1 mg/ml of CFH increasing inulin transfer by 50% without affecting cell viability. CFH (1 mg/ml) also caused a dramatic reduction in intracellular ascorbate in the same time frame (1.4 mM without CFH, 0.23 mM 18 h after 1 mg/ml CFH, p < 0.05). Pre-treatment of HUVECs with ascorbate attenuated CFH induced permeability.Conclusions
CFH increases endothelial permeability in part through depletion of intracellular ascorbate. Supplementation of ascorbate can attenuate increases in permeability mediated by CFH suggesting a possible therapeutic approach in sepsis. 相似文献20.
Iskra H. Bayraktarova Milko K. Stoyanov Boyan T. Kunev Tchavdar N. Shalganov 《Indian pacing and electrophysiology journal》2018,18(2):49-53