A switch toward angiostatic gene expression impairs the angiogenic properties of endothelial progenitor cells in low birth weight preterm infants

Blood ◽  
2011 ◽  
Vol 118 (6) ◽  
pp. 1699-1709 ◽  
Author(s):  
Isabelle Ligi ◽  
Stéphanie Simoncini ◽  
Edwige Tellier ◽  
Paula Frizera Vassallo ◽  
Florence Sabatier ◽  
...  
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Profile Analysis ◽  
Preterm Neonates ◽  
Akt Phosphorylation ◽  
Protein Levels ◽  
Increased Risk ◽  
The Impact

Abstract Low birth weight (LBW) is associated with increased risk of cardiovascular diseases at adulthood. Nevertheless, the impact of LBW on the endothelium is not clearly established. We investigate whether LBW alters the angiogenic properties of cord blood endothelial colony forming cells (LBW-ECFCs) in 25 preterm neonates compared with 25 term neonates (CT-ECFCs). We observed that LBW decreased the number of colonies formed by ECFCs and delayed the time of appearance of their clonal progeny. LBW dramatically reduced LBW-ECFC capacity to form sprouts and tubes, to migrate and to proliferate in vitro. The angiogenic defect of LBW-ECFCs was confirmed in vivo by their inability to form robust capillary networks in Matrigel plugs injected in nu/nu mice. Gene profile analysis of LBW-ECFCs demonstrated an increased expression of antiangiogenic genes. Among them, thrombospondin 1 (THBS1) was highly expressed at RNA and protein levels in LBW-ECFCs. Silencing THBS1 restored the angiogenic properties of LBW-ECFCs by increasing AKT phosphorylation. The imbalance toward an angiostatic state provide a mechanistic link between LBW and the impaired angiogenic properties of ECFCs and allows the identification of THBS1 as a novel player in LBW-ECFC defect, opening new perspectives for novel deprogramming agents.

Abstract 531: Tie-2/Cre--Mediated Conditional Deletion of Lipid Phosphate Phosphatase-3 Reveals Its Role in Endothelial Cell Apoptosis

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Ishita Chatterjee ◽  
Kishore K Wary
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Genome Wide Association Study ◽  
Vascular Endothelial Cell ◽  
Protein Levels ◽  
Conditional Deletion ◽  
Transmission Electron ◽  
Increased Risk

Rationale: A recent genome-wide association study (GWAS) has linked a frequently occurring variation in the LPP3 (also known as PPAP2b) loci to increased risk of coronary heart disease (CAD). However, the in vivo function of LPP3 in vascular endothelial cell is incompletely understood. Goal: To address the endothelial cell (EC) specific function of Lpp3 in mice. Results: Tie-2/Cre mediated Lpp3 deletion did not affect normal vasculogenesis in early embryonic development, in contrast, in late embryonic stages it led to impaired angiogenesis associated with hemorrhage, edema and late embryonic lethal phenotype. Immunohistochemical staining followed by microscopic analyses of mutant embryos revealed reduced fibronectin and VE-cadherin expression throughout different vascular bed, and increased apoptosis in CD31+ vascular structures. Transmission electron microscopy (TEM) showed the presence of apoptotic endothelial cells and disruption of adherens junctions in mutant embryos. LPP3-knockdown in vitro showed an increase in p53 and p21 protein levels, with concomitant decrease in cell proliferation. LPP3-knockdown also decreased transendothelial electrical resistance (TER), interestingly re-expression of ß-catenin cDNA into LPP3-depleted endothelial cells partially restored the effect of loss of LPP3. Conclusion: These results suggest the ability of LPP3 to regulate survival and apoptotic activities of endothelial cells during patho/physiological angiogenesis.

scholarly journals IL-2 administration increases CD4+CD25hi Foxp3+ regulatory T cells in cancer patients

Blood ◽  
2006 ◽  
Vol 107 (6) ◽  
pp. 2409-2414 ◽  
Author(s):  
Mojgan Ahmadzadeh ◽  
Steven A. Rosenberg
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Interleukin 2 ◽  
Selective Inhibition ◽  
High Dose ◽  
Protein Levels ◽  
And Function ◽  
The Impact

Abstract Interleukin-2 (IL-2) is historically known as a T-cell growth factor. Accumulating evidence from knockout mice suggests that IL-2 is crucial for the homeostasis and function of CD4+CD25+ regulatory T cells in vivo. However, the impact of administered IL-2 in an immune intact host has not been studied in rodents or humans. Here, we studied the impact of IL-2 administration on the frequency and function of human CD4+CD25hi T cells in immune intact patients with melanoma or renal cancer. We found that the frequency of CD4+CD25hi T cells was significantly increased after IL-2 treatment, and these cells expressed phenotypic markers associated with regulatory T cells. In addition, both transcript and protein levels of Foxp3, a transcription factor exclusively expressed on regulatory T cells, were consistently increased in CD4 T cells following IL-2 treatment. Functional analysis of the increased number of CD4+CD25hi T cells revealed that this population exhibited potent suppressive activity in vitro. Collectively, our results demonstrate that administration of high-dose IL-2 increased the frequency of circulating CD4+CD25hi Foxp3+ regulatory T cells. Our findings suggest that selective inhibition of IL-2-mediated enhancement of regulatory T cells may improve the therapeutic effectiveness of IL-2 administration. (Blood. 2006;107:2409-2414)

Lack of In Vitro–In Vivo Correlation of Adulthood Cytochrome P450 Activities in Low-Birth-Weight Rats

2014 ◽  
Vol 42 (3) ◽  
pp. 481-481
Author(s):  
Ganesh Cherala ◽  
Jacob Pearson ◽  
Barent DuBois ◽  
Tahir Mahmood
Keyword(s):  
Cytochrome P450 ◽  
Birth Weight ◽  
Low Birth Weight

scholarly journals Association of Serum Creatinine and Electrolyte Abnormalities in Preterm Low Birth Weight Neonates

2017 ◽  
Vol 26 (Number 1) ◽  
pp. 15-20
Author(s):  
Md. S Islam ◽  
M Bhuiyan ◽  
A S Chowdhury ◽  
ATM Rafique ◽  
M Afrin ◽  
...  
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Renal Impairment ◽  
Serum Creatinine ◽  
Preterm Neonates ◽  
Close Monitoring ◽  
Increased Risk ◽  
Electrolyte Abnormalities

Introduction: Being born prematurely is a threat to survival and the subsequent quality of life ICDDR,B Health and Science Bulletin published in March 2006 reported that prematurity and low birth weight contributes to 27.8% of neonatal deaths in rural areas of Bangladesh Premature infant are at increased risk of developing dehydration or over hydration. Therefore, high index of suspicion, prompt recognition and thorough understanding of common electrolyte abnormalities are necessary to improve neonatal outcome. The investigation of renal function in pretenn neonate is complicated because of continuing renal development, rise in creatinine is transient and may not be clinically significcmt. Serum creatinine is most widely used marker of renal function in adults and children but its validity as a marker of GFR/ renal function is doubtful a few studies have been conducted on assessment of renal function and electrolytes in the context of prematurity in Bangladesh. But it seems to be essential for immediate management for planning appropriate fluid and electrolyte therapy and thereby for improved outcome. Information was collected who gave consent and participated in the study willingly. The sample size was 50. Duration of data collection was approximately 6 (Six) months.Patients admitted to the Holy Family Red Crescent Medical College and hospital and after meeting the inclusion and exclusion criteria a simple random sampling technique was applied for selecting the sample patients. Total 50 pretenn LBW neonates fulfilling the inclusion criteria were studied during this study period. Mean creatinine level was .82 mmoKrange was 0.40-1.90 mg/d1. Abnormal electrolytes were documented in 20(40%) pretenn LBW neonates of which hyperkalemia was the predominant electrolyte abnormality found in 8(16.0%) neonates, hyponatremia was found in 7 (14.0%), hypokalemia in 3 (6.0%) and hypernatremia 2 (4.0%). In the present study 20 of preterm LBW babies have electrolyte abnormalities. Hyperkalemia was found in 8(16.0%) babies in this study from above findings it is evident that prematurity causes transient renal impairment, in preterm neonates which is inversely related to gestational age. Renal impairment should be suspected if the serum creatinine rises or fails to show normal post-natal fall. It was observed that electrolyte abnormalities are common in preterm LBW neonates and transient renal failure also occurs in a large number of preterm LBW babies. So, identification of renal failure and associated electrolyte abnormalities and proper management of fluid and electrolytes and close monitoring are important.

scholarly journals Behaviour of Titanium Dioxide Particles in Artificial Body Fluids and Human Blood Plasma

2021 ◽  
Vol 22 (19) ◽  
pp. 10614
Author(s):  
Eva Korábková ◽  
Věra Kašpárková ◽  
Daniela Jasenská ◽  
Dita Moricová ◽  
Eliška Daďová ◽  
...  
Keyword(s):  
Blood Plasma ◽  
Human Blood ◽  
Body Fluids ◽  
Human Blood Plasma ◽  
Tio2 Particles ◽  
Commercial Mixture ◽  
Increased Risk ◽  
The Impact

The growing application of materials containing TiO2 particles has led to an increased risk of human exposure, while a gap in knowledge about the possible adverse effects of TiO2 still exists. In this work, TiO2 particles of rutile, anatase, and their commercial mixture were exposed to various environments, including simulated gastric fluids and human blood plasma (both representing in vivo conditions), and media used in in vitro experiments. Simulated body fluids of different compositions, ionic strengths, and pH were used, and the impact of the absence or presence of chosen enzymes was investigated. The physicochemical properties and agglomeration of TiO2 in these media were determined. The time dependent agglomeration of TiO2 related to the type of TiO2, and mainly to the type and composition of the environment that was observed. The presence of enzymes either prevented or promoted TiO2 agglomeration. TiO2 was also observed to exhibit concentration-dependent cytotoxicity. This knowledge about TiO2 behavior in all the abovementioned environments is critical when TiO2 safety is considered, especially with respect to the significant impact of the presence of proteins and size-related cytotoxicity.

Testosterone augments endotoxin-mediated cerebrovascular inflammation in male rats

2005 ◽  
Vol 289 (5) ◽  
pp. H1843-H1850 ◽  
Author(s):  
Ali Razmara ◽  
Diana N. Krause ◽  
Sue P. Duckles
Keyword(s):  
Blood Vessels ◽  
In Vitro Models ◽  
Male Rats ◽  
Cerebral Blood Vessels ◽  
Treatment Groups ◽  
Protein Levels ◽  
Cox 2 ◽  
The Impact

Activation of inflammatory mechanisms contributes to cerebrovascular pathophysiology. Male gender is associated with increased stroke risk, yet little is known about the effects of testosterone in the cerebral circulation. Therefore, we explored the impact of testosterone treatment on cerebrovascular inflammation with both in vivo and in vitro models of inflammation. We hypothesized that testosterone would augment the expression of two vascular markers of cellular inflammation, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Using four groups of male rats [intact, orchiectomized (ORX), and ORX treated with either testosterone (ORXT) or the testosterone metabolite 17β-estradiol (ORXE)], we determined effects of the sex hormones on cerebrovascular inflammation after intraperitoneal LPS injection. Western blot analysis showed that induction of inflammatory markers was increased in cerebral blood vessels from ORXT rats compared with intact or ORX rats. In contrast, in cerebral blood vessels from ORXE rats, there was a significant decrease in endotoxin-induced COX-2 and iNOS protein levels. Confocal microscopy of cerebral blood vessels from ORXT rats showed increased COX-2 and iNOS immunoreactivity in both endothelial and smooth muscle cells after LPS treatment. In vitro incubation with LPS also induced COX-2 in pial vessels isolated from the four animal treatment groups, with the greatest induction observed in ORXT vessels compared with the ORX and ORXE groups. Production of PGE2, a principal COX-2-derived prostaglandin end product, was also greatest in cerebral vessels isolated from ORXT rats. In conclusion, testosterone increases cerebrovascular inflammation; this effect may contribute to stroke differences between men and women.

scholarly journals Preconception Hemoglobin Concentration and Risk of Low Birth Weight and Small-for-Gestational-Age: A Large Prospective Cohort Study in China

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 271
Author(s):  
Xiaojing Liu ◽  
Hang An ◽  
Nan Li ◽  
Zhiwen Li ◽  
Yali Zhang ◽  
...  
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Prospective Cohort ◽  
Large Population ◽  
Hemoglobin Concentration ◽  
Population Based ◽  
Increased Risk ◽  
The Impact

Less is known about the impact of maternal preconception anemia on birth outcomes. We aimed to examine associations between preconception hemoglobin (Hb) concentrations with risk of low birth weight (LBW) and small-for-gestational-age (SGA). This study was from a large population-based prospective cohort in China and included 124,725 women with singleton live births delivered at gestational ages of 28–45 weeks who were registered before pregnancy. Maternal Hb concentrations were measured during registration, and other health-related information was recorded prospectively. Logistic regression was used to evaluate the associations between preconception Hb concentrations with risk of LBW and SGA, adjusting for potential confounders. The results showed women with preconception anemia accounted for 22.28%. The incidences of LBW/SGA were 2.37%/6.30% among anemic women, and 2.01%/5.48% among non-anemic women, respectively. Preconception mild anemia increased by 17% (95% confidence interval (CI): 1.06, 1.28) and 14% (95% CI: 1.07, 1.21) the risk for LBW and SGA, while moderate-to-severe anemia had no significant association with LBW and SGA. Compared with the 120–129 g/L group, a U-shaped association was observed between preconception Hb concentrations with LBW and SGA. In conclusion, not only maternal anemia but also elevated Hb concentrations before pregnancy contribute to an increased risk of LBW and SGA.

PTEN expression in endothelial cells is down-regulated by uPAR to promote angiogenesis

2015 ◽  
Vol 114 (08) ◽  
pp. 379-389 ◽  
Author(s):  
Matthias Unseld ◽  
Anastasia Chilla ◽  
Clemens Pausz ◽  
Rula Mawas ◽  
Johannes Breuss ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
In Vitro Assays ◽  
Soluble Form ◽  
Dependent Manner ◽  
Drug Interference ◽  
Protein Levels ◽  
Novel Target ◽  
The Impact

SummaryThe tumour suppressor phosphatase and tensin homologue (PTEN), mutated or lost in many human cancers, is a major regulator of angiogenesis. However, the cellular mechanism of PTEN regulation in endothelial cells so far remains elusive. Here, we characterise the urokinase receptor (uPAR, CD87) and its tumour-derived soluble form, suPAR, as a key molecule of regulating PTEN in endothelial cells. We observed uPAR-deficient endothelial cells to express enhanced PTEN mRNA- and protein levels. Consistently, uPAR expression in endogenous negative uPAR cells, down-regulated PTEN and activated the PI3K/Akt pathway. Additionally, we found that integrin adhesion receptors act as trans-membrane signaling partners for uPAR to repress PTEN transcription in a NF-κB-dependent manner. Functional in vitro assays with endothelial cells, derived from uPAR-deficient and PTEN heterozygous crossbred mice, demonstrated the impact of uPAR- dependent PTEN regulation on cell motility and survival. In an in vivo murine angiogenesis model uPAR-deficient PTEN heterozygous animals increased the impaired angiogenic phenotype of uPAR knockout mice and were able to reverse the high invasive potential of PTEN heterozygots. Our data provide first evidence that endogenous as well as exogenous soluble uPAR down-regulated PTEN in endothelial cells to support angiogenesis. The uPAR-induced PTEN regulation might represent a novel target for drug interference, and may lead to the development of new therapeutic strategies in anti-angiogenic treatment.

scholarly journals The impact of the interpregnancy interval on birth weight and other pregnancy outcomes

2012 ◽  
Vol 12 (3) ◽  
pp. 233-241 ◽  
Author(s):  
Abdulbari Bener ◽  
Najah Mohammed Saleh ◽  
Khalil Mohd Khalil Salameh ◽  
Basma Basha ◽  
Sharen Joseph ◽  
...  
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Pregnancy Outcomes ◽  
Interpregnancy Interval ◽  
Normal Delivery ◽  
Face To Face ◽  
Normal Birth ◽  
Increased Risk ◽  
The Impact ◽  
Short Interpregnancy Interval

OBJECTIVES: to investigate the relationship between the interpregnancy interval and low birth weight and other pregnancy outcomes. METHODS: this case-control study was carried out in hospitals from January 2010 to April 2011. For cases, mothers of 1216 newborns with birth weight<2500 g were approached and 854 mothers participated (70.2%). For controls, mothers of 1158 newborns with >2500 g were approached and 854 mothers participated in this study (73.7%). Face-to-face interviews were conducted to complete the questionnaires. RESULTS: of the newborn babies with low birth weight, the risk was higher among mothers with a short interpregnancy interval (40.3%), whereas for infants with normal birth weight, the majority of the mothers had a longer interpregnancy interval of 24 months (44.7%). A short interpregnancy interval of 612 months was more common among women of <25years (49.4%; p<0.001) and those who were illiterate (13.1%; p=0.043) with a higher risk of low birth weight compared to the controls. Prenatal care during the 1st trimester was lower in women with low birth weight children (p<0.001). Normal delivery was observed less in women with a short birth interval among cases (58.7%) compared to controls (79%) (p=0.001). A J-shaped association was observed between low birth weight and the interpregnancy interval. CONCLUSIONS: a short interpregnancy interval is associated with an increased risk of low birth weight, especially in younger and illiterate women.

An ACE inhibitor reduces bactericidal activity of human neutrophils in vitro and impairs mouse neutrophil activity in vivo

2021 ◽  
Vol 13 (604) ◽  
pp. eabj2138
Author(s):  
Duo-Yao Cao ◽  
Jorge F. Giani ◽  
Luciana C. Veiras ◽  
Ellen A. Bernstein ◽  
Derick Okwan-Duodu ◽  
...  
Keyword(s):  
Bactericidal Activity ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Leukotriene B4 ◽  
Human Neutrophils ◽  
Converting Enzyme Inhibitors ◽  
Bacterial Killing ◽  
Increased Risk ◽  
The Impact

Angiotensin-converting enzyme inhibitors (ACEIs) are used by millions of patients to treat hypertension, diabetic kidney disease, and heart failure. However, these patients are often at increased risk of infection. To evaluate the impact of ACEIs on immune responses to infection, we compared the effect of an ACEI versus an angiotensin receptor blocker (ARB) on neutrophil antibacterial activity. ACEI exposure reduced the ability of murine neutrophils to kill methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Klebsiella pneumoniae in vitro. In vivo, ACEI-treated mice infected with MRSA had increased bacteremia and tissue bacteria counts compared to mice treated with an ARB or with no drug. Similarly, ACEIs, but not ARBs, increased the incidence of MRSA-induced infective endocarditis in mice with aortic valve injury. Neutrophils from ACE knockout (KO) mice or mice treated with an ACEI produced less leukotriene B4 (LTB4) upon stimulation with MRSA or lipopolysaccharide, whereas neutrophils overexpressing ACE produced more LTB4 compared to wild-type neutrophils. As a result of reduced LTB4 production, ACE KO neutrophils showed decreased survival signaling and increased apoptosis. In contrast, neutrophils overexpressing ACE had an enhanced survival phenotype. Last, in a cohort of human volunteers receiving the ACEI ramipril for 1 week, ACEI administration reduced neutrophil superoxide and reactive oxygen species production and neutrophils isolated from volunteers during ramipril treatment had reduced bactericidal activity. Together, these data demonstrate that ACEI treatment, but not ARB treatment, can reduce the bacterial killing ability of neutrophils.

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