Endothelial cells of extremely premature infants display impaired immune response after proinflammatory stimulation

Wisgrill, Lukas; Muck, Martina; Wessely, Isabelle; Berger, Angelika; Spittler, Andreas; Förster-Waldl, Elisabeth; Sadeghi, Kambis

doi:10.1038/pr.2017.202

Cited by 12 publications

(11 citation statements)

References 26 publications

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“…We have already taken advantage of this approach in our previous paper to con rm the increased eNOS expression in female ECs [14]. However, the collection of twin cords is limited by a number of criticisms: i) the incidence of spontaneous dizygotic twinning is quite low, around 1-2%; ii) the rate of preterm labour among twins is around 60%; iii) remarkably, HUVECs from premature cords show impaired properties when compared to cells from term cords [72]; iv) intrauterine growth restriction is increased in twin pregnancies [71]; v) about 75% of twins being delivered by cesarean [73]; vi) when childbirth is vaginal, a correlation between twin-to-twin delivery intervals and pH in umbilical arterial blood gas has been found, thus alerting about metabolic acidosis [74]. In addition, it should be considered that some differences may exist between the prenatal environment of male and female dizygotic twins.…”

Section: Limitations Of the Studymentioning

confidence: 99%

Sex-dependent differences in the secretome of human endothelial cells

Cattaneo

Banfi

Brioschi

et al. 2020

Preprint

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Background: Cellular sex has been rarely considered as a biological variable in preclinical research, even when the pathogenesis of diseases with predictable sex differences is studied. In this perspective, proteomics, and ‘omics approaches in general, can provide powerful tools to obtain comprehensive cellular maps, thus favoring the discovery of still unknown sex-biased physio-pathological mechanisms.Methods: We performed proteomic and gene ontology (GO) analyses of secretome from human serum-deprived male and female endothelial cells (ECs) followed by ELISA validation. Apoptosis was detected by FACS and western blot techniques, and efferocytosis through the ability of the macrophage cell line RAW-264.7 to engulf apoptotic ECs. PTX3 mRNA levels were measured by RT-qPCR. Results: Proteomic and GO analyses of the secretome from starved human male and female ECs demonstrated a significant enrichment in proteins related to cellular responses to stress and to the regulation of apoptosis in the secretome of male ECs. Accordingly, a higher percentage of male ECs underwent apoptosis in response to serum deprivation in comparison to female ECs. Among the secreted proteins, we reliably found higher levels of PTX3 in the male EC secretome. The silencing of PTX3 suggests that male ECs were dependent on its expression to properly carry out the efferocytotic process. At variance, female EC efferocytosis seems to be independent on PTX3 expression. Conclusions: Our results demonstrated that serum-starved male and female ECs possess different secretory phenotypes that might take part in the sex-biased response to cellular stress. We identified PTX3 as a crucial player in the male-specific endothelial response to an apoptotic trigger. This novel and sex-related role for secreted proteins, and mainly for PTX3, may open the way to the discovery of still unknown sex-specific mechanisms and pharmacological targets for the prevention and treatment of endothelial dysfunction at the onset of atherosclerosis and cardiovascular disease.

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Section: Limitations Of the Studymentioning

confidence: 99%

Sex-dependent differences in the secretome of human endothelial cells

Cattaneo

Banfi

Brioschi

et al. 2020

Preprint

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“…ECs isolated from fetuses up to 22 weeks of gestational age do not express P-selectin, and intracellular storage of P-selectin in preterm neonates is less than half that of term neonates, at steady state; this, in turn, contributes to the observed defect in rolling, adhesion and crawling of neonatal neutrophils (72). Similarly defective up-regulation of inducible E-selectin, ICAM-1 and VCAM-1 upon LPS stimulation of human umbilical vein ECs (HUVECs) from preterm neonates has been noted (73, 74). Of note, it has also been shown that endothelial selectins, E-selectin and P-selectin, are expressed at least partially during fetal development in humans: in particular, P-selectin seems expressed at adult levels since 11 weeks of gestation while, interestingly, E-selectin reaches adult levels on ECs around 32 weeks (75).…”

Section: Structure Of the Ve In Adults And Neonatesmentioning

confidence: 91%

Vascular Endothelium in Neonatal Sepsis: Basic Mechanisms and Translational Opportunities

et al. 2019

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Neonatal sepsis remains a major health issue worldwide, especially for low-birth weight and premature infants, with a high risk of death and devastating sequelae. Apart from antibiotics and supportive care, there is an unmet need for adjunctive treatments to improve the outcomes of neonatal sepsis. Strong and long-standing research on adult patients has shown that vascular endothelium is a key player in the pathophysiology of sepsis and sepsis-associated organ failure, through a direct interaction with pathogens, leukocytes, platelets, and the effect of soluble circulating mediators, in part produced by endothelial cells themselves. Despite abundant evidence that the neonatal immune response to sepsis is distinct from that of adults, comparable knowledge on neonatal vascular endothelium is much more limited. Neonatal endothelial cells express lower amounts of adhesion molecules compared to adult ones, and present a reduced capacity to neutralize reactive oxygen species. Conversely, available evidence on biomarkers of endothelial damage in neonates is not as robust as in adult patients, and endothelium-targeted therapeutic opportunities for neonatal sepsis are almost unexplored. Here, we summarize current knowledge on the structure of neonatal vascular endothelium, its interactions with neonatal immune system and possible endothelium-targeted diagnostic and therapeutic tools for neonatal sepsis. Furthermore, we outline areas of basic and translational research worthy of further study, to shed light on the role of vascular endothelium in the context of neonatal sepsis.

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“…Although the HUC is formed during the fifth week of gestation, the bioenergetic capacity and immune response of HUVEC, obtained from preterm (<37 weeks of gestation) and full-term infants (37-40 weeks of gestation), are different [60][61][62][63][64]. HUVEC, obtained from preterm infants, show an impaired mitochondrial bioenergy capacity, and increased production of reactive oxygen species (ROS) [64].…”

Section: Umbilical Cord Collection and Conservationmentioning

confidence: 99%

“…Illsinger et al demonstrated that HUVEC mitochondrial enzyme activity changes lead to decreased viability of cells obtained from preterm cords [62]. In addition, the expression of selectins is lower in preterm HUVEC as compared to full-term HUVEC [60,61,63]. All these alterations affect endothelial function [60][61][62][63][64].…”

Section: Umbilical Cord Collection and Conservationmentioning

confidence: 99%

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Use of Human Umbilical Vein Endothelial Cells (HUVEC) as a Model to Study Cardiovascular Disease: A Review

et al. 2020

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Cardiovascular disease (CVD) is the leading cause of death worldwide, and extensive research has been performed to understand this disease better, using various experimental models. The endothelium plays a crucial role in the development of CVD, since it is an interface between bloodstream components, such as monocytes and platelets, and other arterial wall components. Human umbilical vein endothelial cell (HUVEC) isolation from umbilical cord was first described in 1973. To date, this model is still widely used because of the high HUVEC isolation success rate, and because HUVEC are an excellent model to study a broad array of diseases, including cardiovascular and metabolic diseases. We here review the history of HUVEC isolation, the HUVEC model over time, HUVEC culture characteristics and conditions, advantages and disadvantages of this model and finally, its applications in the area of cardiovascular diseases.

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Endothelial cells of extremely premature infants display impaired immune response after proinflammatory stimulation

Cited by 12 publications

References 26 publications

Sex-dependent differences in the secretome of human endothelial cells

Sex-dependent differences in the secretome of human endothelial cells

Vascular Endothelium in Neonatal Sepsis: Basic Mechanisms and Translational Opportunities

Use of Human Umbilical Vein Endothelial Cells (HUVEC) as a Model to Study Cardiovascular Disease: A Review

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