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Results for “Vascularization”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 109 records · Page 6
All sourcesNASA NTRSDOE OSTI
DOE OSTI2026

Enhancers that direct gene expression to central nervous system vascular endothelial cells in vivo

CNS vascular endothelial cells (ECs) exhibit a distinctive gene expression program that is foundational for the blood-brain barrier (BBB). Previous research identified candidate cis-regulatory elements (CREs) that were hypothesized to control this program. In this work, transgenic mice and recombinant adeno-associated virus (rAAV) vectors have been used to interrogate these candidate CREs in vivo. These experiments show that an 850 bp genomic DNA segment ∼60 kb 5′ of Slc2a1 possesses enhancer activity that is (1) specific for BBB+ CNS ECs and (2) both necessary and sufficient for BBB+ EC gene expression. A screen of >8,000 genomic DNA segments from CNS EC-specific CRE candidates reveals several hundred with enhancer activity. Transcription factors ERG and LEF1 are shown to occupy sites in brain ECs that are highly enriched in candidate and experimentally validated CREs, lending strong support to a model in which canonical Wnt signaling activates the BBB program via LEF1.

CUT&RUN↗
DOE OSTI2021

Analysis of a new multispecies tumor growth model coupling 3D phase-fields with a 1D vascular network

In this study, we present and analyze a mathematical model for tumor growth incorporating ECM erosion, interstitial flow, and the effect of vascular flow and nutrient transport. The model is of phase-field or diffused-interface type in which multiple phases of cell species and other constituents are separated by smooth evolving interfaces. The model involves a mesoscale version of Darcy’s law to capture the flow mechanism in the tissue matrix. Modeling flow and transport processes in the vasculature supplying the healthy and cancerous tissue, one-dimensional (1D) equations are considered. Since the models governing the transport and flow processes are defined together with cell species models on a three-dimensional (3D) domain, we obtain a 3D–1D coupled model.

3D–1D coupled blood flow models↗
DOE OSTI2024

Engineering a biopolymer for vascular embolization based on fundamental polymer principals

Herein we describe the engineering of a potential polymer substitute to metal coils for achieving vascular embolization. Our system is based on a methacrylate end-functionalized polyethylene oxide-polypropylene oxide-polyethylene oxide (PEO-PPO-PEO) triblock copolymer which displays thermal-reversible gelation properties and FCC ordering of the original copolymer while also being able to chemically crosslink. This system shows injectability, two-step gelation, chemical crosslinking with a five-fold increase in modulus and is highly resistant to washout under physiological flow conditions. Furthermore, we show that exposure to aqueous flow imparts resistance to swelling where less than 10 % swelling was observed under physiological flow as opposed to more than 60 % under static conditions after 30 days. Auxiliary experiments with PEO-PPO-PEO copolymers of various molecular weights indicate that this phenomenon may possibly be attributed to entanglements known to occur between adjacent micelles, where the reptation time, the time for polymer disentanglement, is long compared to the flow rate.

36 MATERIALS SCIENCE↗
DOE OSTI2021

PDGF-BB-mediated activation of CREB in vascular smooth muscle cells alters cell cycling via Rb, FoxO1 and p27kip1

The vascular response to injury leads to the secretion of several factors, including platelet-derived growth factor (PDGF-BB). PDGF-BB stimulates smooth muscle cell (SMC) conversion to the synthetic phenotype, thereby enhancing proliferation and migration, and contributing to neointimal hyperplasia. Likewise, the cAMP response element binding protein (CREB) transcription factor has been shown to mediate SMC proliferation in response to various mitogens. We therefore investigated the contribution of CREB to PDGF-BB-dependent proliferation of SMCs with the intention of identifying signaling pathways involved both up and downstream of CREB activation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Chorioallantoic membrane vascularization. A meta-analysis

The CAM is a widely used experimental assay to study angiogenesis, wound healing, tumor growth and metastatic process. In this study, we have analyzed and compared the existent literature data concerning the growth of the CAM. Moreover, we have analyzed the data concerning the development of the vascular system and the expression of the most important pro-angiogenic and anti-angiogenic factors. The availability of these data and their comparative evaluation allow to better analyze the experimental data concerning the testing of different pro-angiogenic and anti-angiogenic molecules, as well as biomaterials in the CAM assay. Moreover, the dynamic of the angiogenic response to different tumor cell lines and or tumor bioptic specimens, may be also better evaluated and estimated.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Apelin receptor homodimer inhibits apoptosis in vascular dementia

Apelin receptor (APJ), a member of family A of the G protein-coupled receptors (GPCRs), is a potential pharmaceutical target for diseases of the nervous system. Our previous work revealed that human APJ can form a homodimer that has different functional characteristics than the monomer. To investigate the effects of APJ homodimers on neuroprotection in vascular dementia (VD), we established VD model in rats and treated the animals by injecting apelin-13 into the lateral ventricle. In addition, we established an oxygen–glucose deprivation/reoxygenation (OGD/R) model in SH-SY5Y cells treated with apelin-13. After apelin-13 stimulation in the VD rat, the level of APJ and APJ homodimer were elevated. Furthermore, APJ homodimer decreased the level of cleaved caspase-3 and cleaved caspase-9 via the Gα{sub i3} and Gα{sub q} signaling pathway, thereby increasing the number of neurons and inhibiting apoptosis. Consequently, APJ homodimers may serve as a unique mechanism for neuroprotection against VD and provide new pharmaceutical targets for VD.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Human umbilical cord mesenchymal stem cells regulate CD54 and CD105 in vascular endothelial cells and suppress inflammation in Kawasaki disease

Highlights: • CD31{sup +}CD54{sup +} and CD31{sup +}CD105{sup +} EMPs change inconsistently at different stages of KD, potentially reflect endothelial function. • HucMSCs suppress inflammation and regulate the expression levels of CD54 and CD105 in vascular endothelial cells in KD. • HucMSCs inhibit coronary artery inflammation while also promoting the repair of damaged tissues in KD mice. The objective was to evaluate the expression levels of CD31{sup +}CD54{sup +} and CD31{sup +}CD105{sup +} endothelial microparticles (EMPs) before and after intravenous immunoglobulin (IVIG) treatment of Kawasaki disease (KD). To explore the role of human umbilical cord mesenchymal stem cells (hucMSCs) in inhibiting endothelial inflammation in KD, the effects of hucMSCs on the expression of CD54 and CD105 in endothelial cells in KD were analyzed in vivo and in vitro.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Redox signaling by glutathione peroxidase 2 links vascular modulation to metabolic plasticity of breast cancer

Redox regulation of breast cancer underlies malignant progression. Loss of the antioxidant glutathione peroxidase 2 in breast cancer cells increases reactive oxygen species, thereby activating hypoxia inducible factor-α (HIF1α) signaling. This in turn causes vascular malfunction, resulting in hypoxia and metabolic heterogeneity. HIF1α suppresses oxidative phosphorylation and stimulates glycolysis (the Warburg effect) in most of the tumor, except for one cancer subpopulation, which was capable of using both metabolic modalities. Hence, adopting a hybrid metabolic state may allow tumor cells to survive under aerobic or hypoxic conditions, a vulnerability that may be exploited for therapeutic targeting by either metabolic or redox-based strategies.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

What are grana in chloroplasts of vascular plants good for?

All plants and green algae contain stacked grana thylakoid membranes in their chloroplasts, underscoring an evolutionary pressure to maintain this unique structural feature. In addition, numerous studies have demonstrated that particular lateral and vertical dimensions of grana facilitate the function, regulation and repair of the photosynthetic machinery responsible for energy conversion. In this review, we present an updated overview of our understanding concerning the structure of grana thylakoids, the forces that contribute to their formation and their architectural dynamics. After establishing the structural foundation, we continue by reviewing the implications of grana formation on light harvesting, electron transport and protein maintenance in the thylakoid membranes of vascular plants. Regarding light harvesting, we discuss the implications of grana formation on energy spillover, macromolecular crowding, lateral versus vertical excitation energy transfer, and state transition. With respect to electron transport, we summarize recent findings regarding the functional connectivity of spatially separated photosystems facilitated by grana formation through small mobile electron carriers. We also explore how the dynamic responses of grana architecture regulate electron transport. Finally, we address how grana formation contributes to the organization of protein repair and biogenesis within thylakoid membranes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

A small molecule antagonizes jasmonic acid perception and auxin responses in vascular and nonvascular plants

The phytohormone jasmonoyl-L-isoleucine (JA-Ile) regulates many stress responses and developmental processes in plants. A co-receptor complex formed by the F-box protein Coronatine Insensitive 1 (COI1) and a Jasmonate (JA) ZIM-domain (JAZ) repressor perceives the hormone. JA-Ile antagonists are invaluable tools for exploring the role of JA-Ile in specific tissues and developmental stages, and for identifying regulatory processes of the signaling pathway. Using two complementary chemical screens, we identified three compounds that exhibit a robust inhibitory effect on both the hormone-mediated COI–JAZ interaction and degradation of JAZ1 and JAZ9 in vivo. One molecule, J4, also restrains specific JA-induced physiological responses in different angiosperm plants, including JA-mediated gene expression, growth inhibition, chlorophyll degradation, and anthocyanin accumulation. Interaction experiments with purified proteins indicate that J4 directly interferes with the formation of the Arabidopsis (Arabidopsis thaliana) COI1–JAZ complex otherwise induced by JA. The antagonistic effect of J4 on COI1–JAZ also occurs in the liverwort Marchantia polymorpha, suggesting the mode of action is conserved in land plants. Besides JA signaling, J4 works as an antagonist of the closely related auxin signaling pathway, preventing Transport Inhibitor Response1/Aux–indole-3-acetic acid interaction and auxin responses in planta, including hormone-mediated degradation of an auxin repressor, gene expression, and gravitropic response. However, J4 does not affect other hormonal pathways. Altogether, our results show that this dual antagonist competes with JA-Ile and auxin, preventing the formation of phylogenetically related receptor complexes. J4 may be a useful tool to dissect both the JA-Ile and auxin pathways in particular tissues and developmental stages since it reversibly inhibits these pathways. One-sentence summary: A chemical screen identified a molecule that antagonizes jasmonate perception by directly interfering with receptor complex formation in phylogenetically distant vascular and nonvascular plants.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Feasibility of Vascular Parameter Estimation for Assessing Hypertensive Pregnancy Disorders

Abstract Hypertensive pregnancy disorders (HPDs), such as pre-eclampsia, are leading sources of both maternal and fetal morbidity in pregnancy. Noninvasive imaging, such as ultrasound (US) and magnetic resonance imaging (MRI), is an important tool for predicting and monitoring these high risk pregnancies. While imaging can measure hemodynamic parameters, such as uterine artery pulsatility and resistivity indices (PI and RI), the interpretation of such metrics for disease assessment relies on ad hoc standards, which provide limited insight to the physical mechanisms underlying the emergence of hypertensive pregnancy disorders. To provide meaningful interpretation of measured hemodynamic data in patients, advances in computational fluid dynamics can be brought to bear. In this work, we develop a patient-specific computational framework that combines Bayesian inference with a reduced-order fluid dynamics model to infer parameters, such as vascular resistance, compliance, and vessel cross-sectional area, known to be related to the development of hypertension. The proposed framework enables the prediction of hemodynamic quantities of interest, such as pressure and velocity, directly from sparse and noisy MRI measurements. We illustrate the effectiveness of this approach in two systemic arterial network geometries: an aorta with branching carotid artery and a maternal pelvic arterial network. For both cases, the model can reconstruct the provided measurements and infer parameters of interest. In the case of the maternal pelvic arteries, the model can make a distinction between the pregnancies destined to develop hypertension and those that remain normotensive, expressed through the value range of the predicted absolute pressure.

Biophysics↗
DOE OSTI2024

Renal vascular control during normothermia and passive heat stress does not differ between healthy younger men and women

The mechanisms underlying greater heat-induced acute kidney injury risk in men versus women remain unknown. This study examined renal vascular control, including both vasodilatory (oral protein load) and vasoconstrictor (cold presser test) responses, during normothermia and heat stress and compared these responses between men and women. The results indicated that in both conditions neither renal vasodilatory nor vasoconstrictor responses differ between younger men and younger women.

Physiology↗
DOE OSTI2024

Reliability, stability during long-term storage, and intra-individual variation of circulating levels of osteopontin, osteoprotegerin, vascular endothelial growth factor-A, and interleukin-17A

Background: Studies in many populations have reported associations between circulating cytokine levels and various physiological or pathological conditions. However, the reliability of cytokine measurements in population studies, which measure cytokines in multiple assays over a prolonged period, has not been adequately examined; nor has stability during sample storage or intra-individual variation been assessed. Methods: We assessed (1) analytical reliability in short- and long-term repeated measurements; (2) stability and analytical reliability during long-term sample storage, and (3) variability within individuals over seasons, of four cytokines—osteopontin (OPN), osteoprotegerin (OPG), vascular endothelial growth factor-A (VEGF-A), and interleukin-17A (IL-17A). Measurements in plasma or serum samples were made with commercial kits according to standard procedures. Estimation was performed by fitting a random or mixed effects linear model on the log scale. Results: In repeated assays over a short period, OPN, OPG, and VEGF-A had acceptable reliability, with intra- and inter-assay coefficients of variation (CV) less than 0.11. Reliability of IL-17A was poor, with inter- and intra-assay CV 0.85 and 0.43, respectively. During long-term storage, OPG significantly decayed (-33% per year; 95% confidence interval [-54, -3.7]), but not OPN or VEGF-A (-0.3% or -6.3% per year, respectively). Intra- and inter-assay CV over a long period were comparable to that in a short period except for a slight increase in inter-assay CV of VEGF-A. Within-individual variation was small for OPN and VEGF-A, with intra-class correlations (ICC) 0.68 and 0.83, respectively, but large for OPG (ICC 0.11). Conclusions: We conclude that OPN and VEGF-A can be reliably measured in a large population, that IL-17A is suitable only for small experiments, and that OPG should be assessed with caution due to degradation during storage and intra-individual variation. The overall results of our study illustrate the need for validation under relevant conditions when measuring circulating cytokines in population studies.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Engineered human vascular models to study endothelial dysfunction in infectious disease

Vascular involvement plays a pivotal role in the pathogenesis of numerous emerging viral threats, with climate changes amplifying the likelihood of these diseases evolving into pandemics. Establishing an infectable and physiologically relevant human in vitro model holds immense importance in comprehending the pathogenesis of these threats and devising effective countermeasures. Although in vivo models provide valuable insight into disease, their application is restricted by interspecies variations, particularly concerning pathogens exclusive to humans. Moreover, animal models often fail to replicate comorbidities prevalent in patient populations, thus limiting our understanding of disease behavior in humans. In this study, we have devised a testing platform aimed at exploring pathogen interactions with innate immunity within the vasculature, encompassing both healthy and dysfunctional endothelial conditions.

42 ENGINEERING↗
DOE OSTI2021

Acute Stent-Induced Endothelial Denudation: Biomechanical Predictors of Vascular Injury

Recent concern for local drug delivery and withdrawal of the first Food and Drug Administration-approved bioresorbable scaffold emphasizes the need to optimize the relationships between stent design and drug release with imposed arterial injury and observed pharmacodynamics. In this study, we examine the hypothesis that vascular injury is predictable from stent design and that the expanding force of stent deployment results in increased circumferential stress in the arterial tissue, which may explain acute injury poststent deployment. Using both numerical simulations and ex vivo experiments on three different stent designs (slotted tube, corrugated ring, and delta wing), arterial injury due to device deployment was examined. Furthermore, using numerical simulations, the consequence of changing stent strut radial thickness on arterial wall shear stress and arterial circumferential stress distributions was examined. Regions with predicted arterial circumferential stress exceeding a threshold of 49.5 kPa compared favorably with observed ex vivo endothelial denudation for the three considered stent designs. In addition, increasing strut thickness was predicted to result in more areas of denudation and larger areas exposed to low wall shear stress. We conclude that the acute arterial injury, observed immediately following stent expansion, is caused by high circumferential hoop stresses in the interstrut region, and denuded area profiles are dependent on unit cell geometric features. Such findings when coupled with where drugs move might explain the drug–device interactions.

Conway, Claire↗