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Background: Many trials assessing effects of dietary weight loss on vascular function have been performed without no-weight loss control groups and in individuals with obesity-related morbidities. Usually a limited set of vascular function markers has been investigated. Objective: The objective of this study was to examine effects of diet-induced weight loss on various vascular function markers and differences between normal-weight and abdominally obese men at baseline and after weight reduction. Design: Twenty-five healthy, normal-weight men (waist circumference: <94 cm) and 54 abdominally obese men (waist circumference: 102-110 cm) participated. Abdominally obese participants were randomly allocated to a dietary weight-loss or a no-weight loss control group. Individuals from the weight-loss group followed a calorie-restricted diet for 6 wk to obtain a waist circumference <102 cm followed by a weight-maintenance period of 2 wk. The control group maintained their habitual diet and physical activity levels. The primary outcome was the change in brachial artery flowmediated vasodilation (FMD). Results: Compared with the control group, FMD did not change in the weight-loss group, but carotid-to-femoral pulse wave velocity tended to decrease by 0.5 m/s (P = 0.065). The retinal arteriolar caliber increased by 5 mm (P < 0.001) and the arteriolar-to-venular ratio by 0.02 (P < 0.01). Soluble endothelial selectin and soluble intercellular adhesion molecule concentrations decreased (P < 0.001). Also, total cholesterol, low-density lipoprotein cholesterol, triacylglycerol, glucose, insulin, C-peptide, homeostasis model assessment of insulin resistance, and blood pressure improved (P < 0.05 for all variables). Except for FMD, these markers differed at baseline between normal-weight and abdominally obese men but became comparable after weight loss. Conclusions: In abdominally obese men, dietary weight loss targeting a waist circumference of <102 cm improved retinal microvascular caliber, plasma biomarkers of microvascular endothelial function, and the more conventional cardiometabolic risk markers. Aortic stiffness tended to decrease, but FMD was not changed. [ABSTRACT FROM AUTHOR]

Calcitonin gene-related peptide (CGRP) is a 37-amino-acid neuropeptide belonging to the calcitonin gene peptide superfamily. CGRP is a potent vasodilator with potential therapeutic usefulness for treating vascular-related disease. This peptide is primarily located on C- and Aδ-fibers, which have extensive perivascular presence and a dual sensory-efferent function. Although CGRP has two major isoforms (α-CGRP and β-CGRP), the α-CGRP is the isoform related to vascular actions. Release of CGRP from afferent perivascular nerve terminals has been shown to result in vasodilatation, an effect mediated by at least one receptor (the CGRP receptor). This receptor is an atypical G-protein coupled receptor (GPCR) composed of three functional proteins: (i) the calcitonin receptor-like receptor (CRLR; a seven-transmembrane protein), (ii) the activity-modifying protein type 1 (RAMP1), and (iii) a receptor component protein (RCP). Although under physiological conditions, CGRP seems not to play an important role in vascular tone regulation, this peptide has been strongly related as a key player in migraine and other vascular-related disorders (e.g., hypertension and preeclampsia). The present review aims at providing an overview on the role of sensory fibers and CGRP release on the modulation of vascular tone. [ABSTRACT FROM AUTHOR]

Specific flavonoid-rich foods/beverages are reported to exert positive effects on vascular function; however, data relating to effects in the postprandial state are limited. The present study investigated the postprandial, time-dependent (0–7 h) impact of citrus flavanone intake on vascular function. An acute, randomised, controlled, double-masked, cross-over intervention study was conducted by including middle-aged healthy men (30–65 years, n 28) to assess the impact of flavanone intake (orange juice: 128·9 mg; flavanone-rich orange juice: 272·1 mg; homogenised whole orange: 452·8 mg; isoenergetic control: 0 mg flavanones) on postprandial (double meal delivering a total of 81 g of fat) endothelial function. Endothelial function was assessed by flow-mediated dilatation (FMD) of the brachial artery at 0, 2, 5 and 7 h. Plasma levels of naringenin/hesperetin metabolites (sulphates and glucuronides) and nitric oxide species were also measured. All flavanone interventions were effective at attenuating transient impairments in FMD induced by the double meal (7 h post intake; P<0·05), but no dose–response effects were observed. The effects on FMD coincided with the peak of naringenin/hesperetin metabolites in circulation (7 h) and sustained levels of plasma nitrite. In summary, citrus flavanones are effective at counteracting the negative impact of a sequential double meal on human vascular function, potentially through the actions of flavanone metabolites on nitric oxide. [ABSTRACT FROM AUTHOR]

The arrangement of microvessels in human bone marrow is so far unknown. We combined monoclonal antibodies against CD34 and against CD141 to visualise all microvessel endothelia in 21 serial sections of about 1 cm2 size derived from a human iliac crest. The specimen was not decalcified and embedded in Technovit® 9100. In different regions of interest, the microvasculature was reconstructed in three dimensions using automatic methods. The three-dimensional models were subject to a rigid semiautomatic and manual quality control. In iliac crest bone marrow, the adipose tissue harbours irregularly distributed haematopoietic areas. These are fed by networks of large sinuses, which are loosely connected to networks of small capillaries prevailing in areas of pure adipose tissue. Our findings are compatible with the hypothesis that capillaries and sinuses in human iliac crest bone marrow are partially arranged in parallel. [ABSTRACT FROM AUTHOR]

Nitric oxide-sensitive guanylyl cyclase is a heterodimeric enzyme consisting of an α and a β subunit. Two different α subunits (α 1 and α 2 ) give rise to two heterodimeric enzymes α 1 /β 1 and α 2 /β 1 . Both coexist in a wide range of tissues including blood vessels and the lung, but expression of the α 2 /β 1 form is generally much lower and approaches levels similar to the α 1 /β 1 form in the brain only. In the present paper, we show that the α 2 /β 1 form interacts with Lin7a in mouse brain synaptosomes based on co-precipitation analysis. In HEK293 cells, we found that the overexpressed α 2 /β 1 form, but not the α 1 /β 1 form is directed to calcium-insensitive cell-cell contacts. The isolated PDZ binding motif of an amino-terminally truncated α 2 subunit was sufficient for cell-cell contact localization. For the full length α 2 subunit with the PDZ binding motif this was only the case in the heterodimer configuration with the β 1 subunit, but not as isolated α 2 subunit. We conclude that the PDZ binding motif of the α 2 subunit is only accessible in the heterodimer conformation of the mature nitric oxide-sensitive enzyme. Interaction with Lin7a, a small scaffold protein important for synaptic function and cell polarity, can direct this complex to nectin based cell-cell contacts via MPP3 in HEK293 cells. We conclude that heterodimerization is a prerequisite for further protein-protein interactions that direct the α 2 /β 1 form to strategic sites of the cell membrane with adjacent neighbouring cells. Drugs increasing the nitric oxide-sensitivity of this specific form may be particularly effective. [ABSTRACT FROM AUTHOR]

Aims: Circulating angiogenic cells (CACs) promote revascularization of ischaemic tissues although their underlying mechanism of action and the consequences of delivering varying number of these cells for therapy remain unknown. This study investigates molecular mechanisms underpinning CAC modulation of blood vessel formation. Methods and results: CACs at low (2 x 105 cells/mL) and mid (2 x 106 cells/mL) cellular densities significantly enhanced endothelial cell tube formation in vitro, while high density (HD) CACs (2 x 107 cells/mL) significantly inhibited this angiogenic process. In vivo, Matrigel-based angiogenesis assays confirmed mid-density CACs as pro-angiogenic and HD CACs as anti-angiogenic. Secretome characterization of CAC-EC conditioned media identified pentraxin 3 (PTX3) as only present in the HD CAC-EC co-culture. Recombinant PTX3 inhibited endothelial tube formation in vitro and in vivo. Importantly, our data revealed that the anti-angiogenic effect observed in HD CAC-EC co-cultures was significantly abrogated when PTX3 bioactivity was blocked using neutralizing antibodies or PTX3 siRNA in endothelial cells. We show evidence for an endothelial source of PTX3, triggered by exposure to HD CACs. In addition, we confirmed that PTX3 inhibits fibroblast growth factor (FGF) 2-mediated angiogenesis, and that the PTX3 N-terminus, containing the FGF-binding site, is responsible for such anti-angiogenic effects. Conclusion: Endothelium, when exposed to HD CACs, releases PTX3 which markedly impairs the vascular regenerative response in an autocrine manner. Therefore, CAC density and accompanying release of angiocrine PTX3 are critical considerations when using these cells as a cell therapy for ischaemic disease. [ABSTRACT FROM AUTHOR]

Aims: Stent deployment causes endothelial cells (EC) denudation, which promotes in-stent restenosis and thrombosis. Thus endothelial regrowth in stented arteries is an important therapeutic goal. Stent struts modify local hemodynamics, however the effects of flow perturbation on EC injury and repair are incompletely understood. By studying the effects of stent struts on flow and EC migration, we identified an intervention that promotes endothelial repair in stented arteries. Methods and Results: In vitro and in vivo models were developed to monitor endothelialization under flow and the influence of stent struts. A 2D parallel-plate flow chamber with 100 μm ridges arranged perpendicular to the flow was used. Live cell imaging coupled to computational fluid dynamic simulations revealed that EC migrate in the direction of flow upstream from the ridges but subsequently accumulate downstream from ridges at sites of bidirectional flow. The mechanism of EC trapping by bidirectional flow involved reduced migratory polarity associated with altered actin dynamics. Inhibition of Rho-associated protein kinase (ROCK) enhanced endothelialization of ridged surfaces by promoting migratory polarity under bidirectional flow (P<0.01). To more closely mimic the in vivo situation, we cultured EC on the inner surface of polydimethylsiloxane tubing containing Coroflex Blue stents (65 μm struts) and monitored migration. ROCK inhibition significantly enhanced EC accumulation downstream from struts under flow (P<0.05). We investigated the effects of ROCK inhibition on re-endothelialization in vivo using a porcine model of EC denudation and stent placement. En face staining and confocal microscopy revealed that inhibition of ROCK using fasudil (30 mg/day via osmotic minipump) significantly increased re-endothelialization of stented carotid arteries (P<0.05). Conclusions: Stent struts delay endothelial repair by generating localized bidirectional flow which traps migrating EC. ROCK inhibitors accelerate endothelial repair of stented arteries by enhancing EC polarity and migration through regions of bidirectional flow. [ABSTRACT FROM AUTHOR]

Histological studies of the lymphatic vascular system in adult mice are hampered because bones cannot be sectioned properly. Here, we decalcified the heads of 14-day-old mice, embedded them in paraffin and stained resultant serial sections with the lymphendothelial-specific antibodies Lyve-1 and Podoplanin. We show that the tissues with the highest lymphatic vascular density are the dermis and the oral mucous membranes. In contrast, the nasal mucous membrane is devoid of lymphatics, except for its most basal parts below the vomeronasal organ. The inferior nasal turbinate contains numerous lymphatics and is connected to the nasolacrimal duct (NLD), which is ensheathed by a dense network of lymphatics. The lymphatics of the eye lids and conjunctiva are connected to those of the inferior nasal turbinate. We suggest that cerebro-spinal fluid (CSF) can drain via the optic nerve and NLD lymphatics, whereas CSF drained via the Fila olfactoria into the nasal mucous membrane is used for moisturization of the respiratory air. Tongue, palatine and buccal mucous membranes possess numerous lymphatics, whereas the dental pulp has none. Lymphatics are present in the maxillary gland and close to the temporomandibular joint, suggesting the augmentation of lymph flow by chewing and yawning. Lymphatics can also be found in the dura mater and in the dural septae entering into deeper parts of the brain. Our findings are discussed with regard to CSF drainage and potential routes for ocular tumor dissemination. [ABSTRACT FROM AUTHOR]

SIRT1 has many important molecular functions in aging, and the estrogen receptors ( ERs) have a vasculoprotective effect, although the detailed mechanism for the roles of SIRT1 and ERs in vascular aging remains unclear. We found that ERβ expression in the endothelium was reduced in aging mice, and the expression of ERα and SIRT1 did not change, while SIRT1 activity declined. Further investigation showed that the ERβ expression was regulated by SIRT1 through complexes of SIRT1- PPARγ/ RXR-p300 that bind to a PPRE ( PPAR response element) site on the ERβ promoter, and the declined SIRT1 function in aging mice was due to compromised phosphorylation at S154. A single-mutant SIRT1-C152(D) restored the reduced ERβ expression in the endothelium with minimized reactive oxygen species generation and DNA damage and increased mitochondrial function and fatty acid metabolism. In high-fat diet aging mice, the endothelium-specific delivery of ERβ or SIRT1-C152(D) on the vascular wall reduced the circulating lipids with ameliorated vascular damage, including the restored vessel tension and blood pressure. We conclude that SIRT1-mediated ERβ suppression in the endothelium contributes to vascular aging, and the modulation of SIRT1 phosphorylation through a single-mutant SIRT1-C152(D) restores this effect. [ABSTRACT FROM AUTHOR]

A novel theoretical method is presented for simulating the spatially resolved convective and diffusive transport of reacting solutes between microvascular networks and the surrounding tissues. The method allows for efficient computational solution of problems involving convection and non-linear binding of solutes in blood flowing through microvascular networks with realistic 3D geometries, coupled with transvascular exchange and diffusion and reaction in the surrounding tissue space. The method is based on a Green's function approach, in which the solute concentration distribution in the tissue is expressed as a sum of fields generated by time-varying distributions of discrete sources and sinks. As an example of the application of the method, the washout of an inert diffusible tracer substance from a tissue region perfused by a network of microvessels is simulated, showing its dependence on the solute's transvascular permeability and tissue diffusivity. Exponential decay of the washout concentration is predicted, with rate constants that are about 10-30% lower than the rate constants for a tissue cylinder model with the same vessel length, vessel surface area and blood flow rate per tissue volume. [ABSTRACT FROM AUTHOR]

Intrauterine growth restriction (IUGR) is a common pregnancy complication and is a leading cause of fetal morbidity and mortality. Placental hypoxia contributes to adverse fetal consequences, such as IUGR. Exposing pregnant rats to hypoxia can lead to IUGR; however, assessment of maternal vascular function in a rat model of hypoxia, and the mechanisms that may contribute to adverse pregnancy outcomes, has not been extensively studied. We hypothesized that exposing pregnant rats to hypoxia will affect maternal systemic vascular function and increase the uterine artery resistance index (RI), which will be associated with IUGR. To test this hypothesis, pregnant rats were kept in normoxia (21% O2) or hypoxia (11% O2) from gestational day (GD) 6 to 20. Maternal blood pressure, uteroplacental resistance index (RI) (ultrasound biomicroscopy), and vascular function (wire myography) were assessed in uterine and mesenteric arteries. Fetal weight was significantly reduced (P < 0.001), while maternal blood pressure was increased (P < 0.05) in rats exposed to hypoxia. Maternal vascular function was also affected after exposure to hypoxia, including impaired endothelium-dependent vasodilation responses to methacholine in isolated uterine arteries (pEC50 normoxia: 6.55 ± 0.23 vs. hypoxia: 5.02 ± 0.35, P < 0.01) and a reduced uterine artery RI in vivo (normoxia: 0.63 ± 0.04 vs. hypoxia: 0.53 ± 0.01, P < 0.05); associated with an increase in umbilical vein RI (normoxia: 0.35 ± 0.02 vs. hypoxia: 0.45 ± 0.04, P < 0.05). These data demonstrate maternal and fetal alterations in vascular function due to prenatal exposure to hypoxia. Further, although there was a compensatory reduction in uterine artery RI in the hypoxia groups, this was not sufficient to prevent IUGR. [ABSTRACT FROM AUTHOR]

Neoadjuvant chemotherapy (NAC) followed by hysterectomy may be effective for the treatment of locally advanced uterine cervical cancer and improve patient prognosis. It is important to identify markers that are able to predict whether NAC may be successful. Epidermal growth factor-like domain 7 (EGFL7) regulates vascular sprouting in blood vessel formation. In numerous types of human cancer, EGFL7 is upregulated and inhibits endothelial cell adhesion molecules, decreasing vascular tightness and, thus, increasing vascular permeability. It is considered that the overexpression of EGFL7 is able to inhibit drug delivery, resistance to apoptosis and the epithelial-to-mesenchymal transition. In the current study, 63 patients with locally advanced uterine cervical cancer were reviewed and classified as stage IIIA-IIIB using the International Federation of Gynecology and Obstetrics criteria. These patients (aged <70 years) were treated at Osaka City University Medical School Hospital, Japan, between 1995 and 2010. Tumor tissue samples were obtained by biopsy prior to NAC. The tissue samples were classified as group 1 or 2 depending on the efficacy of NAC. Surgery and radiotherapy were administered in group 1 (n=36), for which NAC was effective. In the patients of group 2 NAC was not effective, and radiotherapy alone was administered (n=27). The expression of EGFL7 and Snail was examined in paraffin-embedded tissue sample sections using the avidin-biotin peroxidase complex method. The results indicated that EGFL7 expression levels were significantly higher in group 2, as compared with group 1 (P<0.001). A similar result was observed for the expression levels of Snail (P=0.001). Group 1 exhibited significantly longer overall survival times compared with group 2 (P=0.001). The patients were also classified into a low EGFL7 expression level group (weighted score of =6) and a high EGFL7 expression level group (weighted score of =8). NAC was observed to be significantly more effective in the low EGFL7 expression level group (P<0.001), as compared with the high expression level group. The results suggest that the expression levels of EGFL7 may be a potential predictive marker of the efficacy of NAC for the treatment of locally advanced uterine cervical cancer. [ABSTRACT FROM AUTHOR]

Extant crocodilians are a highly apomorphic archosaur clade that is ectothermic, yet often achieve large body sizes that can be subject to higher heat loads. Therefore, the anatomical and physiological roles that blood vessels play in crocodilian thermoregulation need further investigation to better understand how crocodilians establish and maintain cephalic temperatures and regulate neurosensory tissue temperatures during basking and normal activities. The cephalic vascular anatomy of extant crocodilians, particularly American alligator ( Alligator mississippiensis) was investigated using a differential-contrast, dual-vascular injection technique and high resolution X-ray micro-computed tomography (μ CT). Blood vessels were digitally isolated to create representations of vascular pathways. The specimens were then dissected to confirm CT results. Sites of thermal exchange, consisting of the oral, nasal, and orbital regions, were given special attention due to their role in evaporative cooling and cephalic thermoregulation in other diapsids. Blood vessels to and from sites of thermal exchange were studied to detect conserved vascular patterns and to assess their ability to deliver cooled blood to neurosensory tissues. Within the orbital region, both the arteries and veins demonstrated consistent branching patterns, with the supraorbital, infraorbital, and ophthalmotemporal vessels supplying and draining the orbit. The venous drainage of the orbital region showed connections to the dural sinuses via the orbital veins and cavernous sinus. The palatal region demonstrated a vast plexus that comprised both arteries and veins. The most direct route of venous drainage of the palatal plexus was through the palatomaxillary veins, essentially bypassing neurosensory tissues. Anastomotic connections with the nasal region, however, may provide an alternative route for palatal venous blood to reach neurosensory tissues. The nasal region in crocodilians is probably the most prominent site of thermal exchange, as it offers a substantial surface area and is completely surrounded by blood vessels. The venous drainage routes from the nasal region offer routes directly to the dural venous sinuses and the orbit, offering evidence of the potential to directly affect neurosensory tissue temperatures. The evolutionary history of crocodilians is complex, with large-bodied, terrestrial, and possibly endothermic taxa that may have had to deal with thermal loads that likely provided the anatomical building-blocks for such an extensive vascularization of sites of thermal exchange. A clear understanding of the physiological abilities and the role of blood vessels in the thermoregulation of crocodilians neurosensory tissues is not available but vascular anatomical patterns of crocodilian sites of thermal exchange indicate possible physiological abilities that may be more sophisticated than in other extant diapsids. [ABSTRACT FROM AUTHOR]

Highlights • Active hydrophobic spots produce nanobubbles in all blood vessels. • Nitrogen tension in the distal arteries increases on decompression. • Nanobubbles in a distal artery grow during each breath-hold dive causing taravana. • Low vestibular organ perfusion enables nanobubbles to gain N 2 causing vestibular DCI. Abstract Decompression bubbles can develop only from pre-existing gas micronuclei. These are the nanobubbles which appear on active hydrophobic spots (AHS) found on the luminal aspect of all blood vessels. Following decompression, with the propagation of blood along the arterial tree, diffusion parameters cause increased transfer of nitrogen from the tissue into the artery, and more so if perfusion is low. Taravana is a neurological form of decompression illness (DCI) prevalent in repeated breath-hold diving. A nanobubble on an AHS in a distal artery of the brain may receive an influx of nitrogen after each dive until it occludes the arterial blood flow. The vestibular organ has very low perfusion compared with the brain and the cochlea of the inner ear. We suggest that a nanobbubble on an AHS in the distal artery of the vestibular organ will receive a high influx of nitrogen from the surrounding tissue after decompression due to the low nitrogen clearance, thus expanding to cause vestibular DCI. [ABSTRACT FROM AUTHOR]

Angiogenesis involves the formation of new blood vessels by sprouting or splitting of existing blood vessels. During sprouting, a highly motile type of endothelial cell, called the tip cell, migrates from the blood vessels followed by stalk cells, an endothelial cell type that forms the body of the sprout. To get more insight into how tip cells contribute to angiogenesis, we extended an existing computational model of vascular network formation based on the cellular Potts model with tip and stalk differentiation, without making a priori assumptions about the differences between tip cells and stalk cells. To predict potential differences, we looked for parameter values that make tip cells (a) move to the sprout tip, and (b) change the morphology of the angiogenic networks. The screening predicted that if tip cells respond less effectively to an endothelial chemoattractant than stalk cells, they move to the tips of the sprouts, which impacts the morphology of the networks. A comparison of this model prediction with genes expressed differentially in tip and stalk cells revealed that the endothelial chemoattractant Apelin and its receptor APJ may match the model prediction. To test the model prediction we inhibited Apelin signaling in our model and in an in vitro model of angiogenic sprouting, and found that in both cases inhibition of Apelin or of its receptor APJ reduces sprouting. Based on the prediction of the computational model, we propose that the differential expression of Apelin and APJ yields a “self-generated” gradient mechanisms that accelerates the extension of the sprout. [ABSTRACT FROM AUTHOR]

The anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) are a heterogeneous group of diseases causing inflammation in small blood vessels and linked by the presence of circulating ANCA specific for proteinase 3 (PR3) or myeloperoxidase (MPO). These antigens are present both in the cytoplasmic granules and on the surface of neutrophils, and the effect of ANCA on neutrophil biology has been extensively studied. In contrast, less attention has been paid to the role of monocytes in AAV. These cells contain PR3 and MPO in lysosomes and can also express them at the cell surface. Monocytes respond to ANCA by producing pro-inflammatory and chemotactic cytokines, reactive-oxygen-species and by up-regulating CD14. Moreover, soluble and cell surface markers of monocyte activation are raised in AAV patients, suggesting an activated phenotype that may persist even during disease remission. The presence of monocyte-derived macrophages and giant cells within damaged renal and vascular tissue in AAV also attests to their role in pathogenesis. In particular, their presence in the tertiary lymphoid organ-like granulomas of AAV patients may generate an environment predisposed to maintaining autoimmunity. Here we discuss the evidence for a pathogenic role of monocytes in AAV, their role in granuloma formation and tissue damage, and their potential to both direct and maintain autoimmunity. ANCA-activation of monocytes may therefore provide an explanation for the relapsing–remitting course of disease and its links with infections. Monocytes may thus represent a promising target for the treatment of this group of life-threatening diseases. [ABSTRACT FROM AUTHOR]

Additive manufacturing (AM), sometimes called three-dimensional (3D) printing, has attracted a lot of research interest and is presenting unprecedented opportunities in biomedical fields, because this technology enables the fabrication of biomedical constructs with great freedom and in high precision. An important strategy in AM of biomedical constructs is to mimic the structural organizations of natural biological organisms. This can be done by directly depositing cells and biomaterials, depositing biomaterial structures before seeding cells, or fabricating molds before casting biomaterials and cells. This review organizes the research advances of AM-based biomimetic biomedical constructs into three major directions: 3D constructs that mimic tubular and branched networks of vasculatures; 3D constructs that contains gradient interfaces between different tissues; and 3D constructs that have different cells positioned to create multicellular systems. Other recent advances are also highlighted, regarding the applications of AM for organs-on-chips, AM-based micro/nanostructures, and functional nanomaterials. Under this theme, multiple aspects of AM including imaging/characterization, material selection, design, and printing techniques are discussed. The outlook at the end of this review points out several possible research directions for the future. [ABSTRACT FROM AUTHOR]

Background: Exercise training (ExT) prompts multiple beneficial adaptations associated with vascular health, such as increases in skeletal muscle capillarization and vascular dilator function and decreases in arterial stiffness. However, whether ExT performed in hypoxic conditions induces enhanced effects is unclear. Objective: We sought to systematically review the literature and determine whether hypoxic ExT leads to superior vascular adaptations compared with normoxic ExT. Methods: We searched MEDLINE, Scopus, and Web of Science from their inception until September 2015 for articles assessing vascular adaptations to ExT performed under hypoxic and normoxic conditions. We performed meta-analyses to determine the standardized mean difference (SMD) between the effects of ExT performed in hypoxia versus normoxia on vascular adaptations. We assessed heterogeneity among studies using I statistics and evaluated publication bias via the Begg and Mazumdar's rank correlation test and Egger's regression test. Results: After systematic review, we included 21 controlled studies, including a total of 331 individuals (mean age 19-57 years, 265 males). ExT programs primarily consisted of cycling endurance training performed in normobaric hypoxia or normoxia; duration ranged from 3 to 10 weeks. The exercise intensity was similar in relative terms in the groups trained in hypoxia and normoxia in the majority of studies (17 of 21). After data pooling, skeletal muscle capillarization ( n = 182, SMD = 0.40, 95 % confidence interval [CI] 0.10-0.70; P = 0.01) and vascular dilator function ( n = 71, SMD = 0.67, 95 % CI 0.17-1.18; P = 0.009) but not arterial stiffness ( n = 112, SMD = −0.03, 95 % CI −0.69 to 0.63; P = 0.93), were enhanced with ExT performed in hypoxia versus normoxia. We only found heterogeneity among studies assessing arterial stiffness ( I = 63 %, P = 0.02), and no publication bias was detected. Conclusion: Based on current published studies, hypoxic ExT potentiates vascular adaptations related to skeletal muscle capillarization and dilator function. These findings may contribute to establishing effective exercise programs designed to enhance vascular health. [ABSTRACT FROM AUTHOR]

Purpose: To explore whether superb microvascular imaging (SMI) technology could be helpful for the evaluation of hepatic tumors.Materials and Methods: Our institutional review board approved this study, and informed consent was obtained from all of the patients. Twenty-three patients with 29 hepatic tumors were enrolled in our study. The tumors consisted of hemangiomas (n=15), focal nodular hyperplasias (FNHs) (n=7), and hepatocellular carcinomas (n=7). All lesions were pathologically (n=2) or radiologically (n=27) confirmed. The mean tumor diameter was 1.9cm (range, 0.9cm to 5.0cm). Using SMI technology, all lesions were scanned and categorized into subgroups according to the flow pattern on the SMI.Results: The hemangiomas exhibited nodular rim patterns (33%) and spotty dot-like patterns (20%), and both of these findings were very specific for the diagnosis of hemangioma. The FNHs exhibited spoke-wheel patterns (43%) and radiating vessel patterns (29%) that were very specific findings for the diagnosis of FNH. The other tumors did not exhibit any specific patterns on SMI.Conclusion: Evaluations of the inner vascularities of hepatic tumors with the SMI technique were feasible, and the SMI features were significantly different between the different types of hepatic tumors. These differences could aid the diagnoses of hepatic tumors with US. [ABSTRACT FROM AUTHOR]

In the past decade, significant advances have been made in the design and optimization of novel biomaterials and microfabrication techniques to generate vascularized tissues. Novel microfluidic systems have facilitated the development and optimization of in vitro models for exploring the complex pathophysiological phenomena that occur inside a microvascular environment. To date, most of these models have focused on engineering of increasingly complex systems, rather than analyzing the molecular and cellular mechanisms that drive microvascular network morphogenesis and remodeling. In fact, mutual interactions among endothelial cells (ECs), supporting mural cells and organ-specific cells, as well as between ECs and the extracellular matrix, are key driving forces for vascularization. This review focuses on the integration of materials science, microengineering and vascular biology for the development of in vitro microvascular systems. Various approaches currently being applied to study cell-cell/cell-matrix interactions, as well as biochemical/biophysical cues promoting vascularization and their impact on microvascular network formation, will be identified and discussed. Finally, this review will explore in vitro applications of microvascular systems, in vivo integration of transplanted vascularized tissues, and the important challenges for vascularization and controlling the microcirculatory system within the engineered tissues, especially for microfabrication approaches. It is likely that existing models and more complex models will further our understanding of the key elements of vascular network growth, stabilization and remodeling to translate basic research principles into functional, vascularized tissue constructs for regenerative medicine applications, drug screening and disease models. [ABSTRACT FROM AUTHOR]

The aim was to identify the factors influencing intracranial vessel density (VD). The Hounsfield units of the dense vessel and the contralateral side were measured in 34 patients with arterial clots, 20 with venous clots, and 196 without clots and correlated with skull thickness, density and dimensions, gender, age, red blood cell count (RBC), hemoglobin (HB), hematocrit (HT), creatinine, and sodium. Positive correlations were found between VD and HT, RBC, HB, creatinine, and occipital bone density. Density differences between the right and left intracranial vessels were more accurate (sensitivity/specificity/accuracy=0.91/0.93/0.93 and 0.75/0.87/0.85, respectively) for detecting clots than VD alone. HT, RBC, and HB are the main factors that correlate with VD. [ABSTRACT FROM AUTHOR]

Background: The rationale of this study is to determine alterations in blood rheology (erythrocyte aggregation and deformability) and relationship between structural measurements obtained from optical coherence tomography (OCT) in different stages of primary open angle glaucoma (POAG).Methods: This prospective controlled study comprised 23 POAG patients (glaucoma group) and 23 age- and sex-matched healthy subjects (control group). Elongation index (EI), which is the indicator of erythrocyte deformability and erythrocyte aggregation was measured using an ektacytometer. Optic nerve head (ONH) morphology and peripapillary retinal nerve fibre layer (RNFL) thickness were evaluated using a spectral domain (SD) OCT.Results: There were no significant differences between the groups regarding the elongation index values (p > 0.05). On the other hand, erythrocyte aggregation amplitude (AMP) and mean corpuscular haemoglobin concentration (MCHC) were significantly higher in the glaucoma group than in the control group (p = 0.015, p = 0.003 respectively). A significant correlation was also found between the elongation index and retinal nerve fibre layer (average and superior) thickness (p < 0.05) in patients with late glaucoma.Conclusions: In patients with POAG, erythrocyte aggregation appears to be higher. It can be speculated that higher erythrocyte aggregation and deformability may be involved in the pathogenesis of glaucoma by affecting microperfusion of the optic nerve head and retina. Modification of rheological parameters in patients with glaucoma may be considered as an adjuvant future therapy in glaucoma management, whereas further studies in larger groups are needed. [ABSTRACT FROM AUTHOR]

The vertebral arteries (VAs) are anatomically divided into four segments (V 1 -V 4 ), which cumulatively transport blood flow through neck and ultimately form the posterior circulation of the brain. The vital physiological function of these conduit vessels depends on their geometry, composition and mechanical properties, all of which may vary among the defined arterial segments. Despite their significant role in blood circulation and susceptibility to injury, few studies have focused on characterizing the mechanical properties of VAs, and none have investigated the potential for segmental variation that could arise due to distinct perivascular environments. In this study, we compare the passive mechanical response of the central, juxtaposed arterial segments of porcine VAs (V 2 and V 3 ) via inflation-extension mechanical testing. Obtained experimental data and histological measures of arterial wall composition were used to adjust parameters of structure-motivated constitutive models that quantify the passive mechanical properties of each arterial segment and enable prediction of wall stress distributions under physiologic loads and boundary conditions. Our findings reveal significant segmental differences in the arterial wall geometry and structure. Nevertheless, similar wall stress distributions are predicted in these neighboring arterial segments if calculations account for their specific perivascular environments. These findings allow speculation that segmental differences in wall structure and geometry are a consequence of a previously introduced principle of optimal operation of arteries, which ensures effective bearing of physiological load and a favorable mechanical environment for mechanosensitive vascular smooth muscle cells. Statement of Significance Among the numerous biomechanical investigations devoted to conduit blood vessels, only a few deal with vertebral arteries. While these studies provide useful information that describes the vessel mechanical response, they do not enable identification of a constitutive formulation of the mechanical properties of the vessel wall. This is an important distinction, as a constitutive material model is required to calculate the local stress environment of mechanosensitive vascular cells and fully understand the mechanical implications of both vascular injury and clinical intervention. Moreover, segmental differences in the mechanical properties of the vertebral arteries could be used to discriminate among distinct modes of injury and disease etiologies. [ABSTRACT FROM AUTHOR]

Background: Acai (Euterpe oleracea) is a polyphenol-rich fruit marketed as beneficial for health. Experimental data showing improvements in health markers arising from açai consumption in humans is limited. Objective: The objective of the present study was to investigate the effect of açai consumption on acute changes in vascular function and on other disease risk markers, including postprandial plasma insulin, glucose, and oxidative stress. Design: Twenty-three healthy male volunteers, aged 30-65 y and with a body mass index (in kg/m²) of 25-30, completed a randomized, controlled, high-fat challenge, double-blind, crossover, acute dietary intervention trial. The volunteers consumed either an açai-based smoothie (AS) or a macronutrient-matched control smoothie (PS) together with a high-fat breakfast meal challenge. The primary endpoint was the assessment of endothelial function in the brachial artery by flow-mediated dilatation (FMD). Results: The acute consumption of an AS containing 694 mg total phenolics improved vascular function, with postprandial increases in FMD from baseline of 1.4% at 2 h compared with 0.4% after consumption of the PS (P = 0.001) and increases at 6 h of 0.8% for the AS compared with -0.3% for the PS (P, 0.001). There was also a significantly lower incremental area under the curve (iAUC) for total peroxide oxidative status after açai consumption relative to the control. No significant changes were observed in blood pressure, heart rate, or postprandial glucose response. However, the first postprandial insulin peak (after breakfast) and the iAUC for insulin were elevated for the AS relative to the PS. Conclusions: In this acute study in overweight men, açai consumption was associated with improvements in vascular function, which may lower the risk of a cardiovascular event. Future intervention studies, perhaps with a chronic design, in wider populations and with other biomarkers of disease risk are needed to fully elucidate the benefits of açai to health. This trial was registered at clinicaltrials. gov as NCT02292329. [ABSTRACT FROM AUTHOR]

Background: During oxaliplatin chemotherapy administration via a peripheral vein, vascular pain requires changing of the intravenous infusion route on occasion. Vascular pain induced by anticancer drugs reduces the rate of patient continuation and completion of chemotherapy. Pain is presently appraised using subjective methods, such as the visual analog scale (VAS). However, because pain evaluation can vary depending on the physical state and mood of the patient at the time of assessment, it is desirable to evaluate pain objectively. PainVision PS-2100 (PV) is a medical device that was designed to objectively and quantitatively assess patient nociception and perception. Methods: The present study examined the correlation of subjective and objective assessment of oxaliplatin-induced vascular pain using VAS and PV, respectively. Results: Vascular pain was assessed using both PV and VAS a total of 173 times for 58 colorectal cancer patients. Partial correlation analysis was performed to evaluate the relationship between PV and VAS. The mean PV and VAS scores were 44.5 (range: 0-596) and 24.8 (range: 0-100), respectively. The partial correlation coefficient was 0.408 (p < 0.0001). Conclusions: A strong correlation was not observed between the results, and a weak correlation was observed between VAS and PV scores. Objective evaluation of oxaliplatin-induced vascular pain will be required to help patients overcome vascular pain. [ABSTRACT FROM AUTHOR]

Background. Vasculogenic mimicry can promote tumor growth and metastasis. This article is aimed at conducting a systematic meta-analysis to explore the clinicopathological and prognostic significance of vasculogenic mimicry and gastric cancer. Methods. We searched Pubmed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and the VIP and Wanfang Database for eligible studies. We manually searched for printed journals and relevant textbooks. Subgroups analyses were performed based on the region, manuscript quality, methods of vasculogenic mimicry identification, pathology, and number of patients. Results. Nine studies with 997 patients were included in this meta-analysis. A significant association was observed between vasculogenic mimicry-positive patients and those with gastric cancer with poor overall survival (hazard ratio = 2.24, 95% confidence interval: 1.45–3.47), poor pathological grading, high tumor node metastasis clinical stage, lymph node metastasis, deep tumor invasion, and distant metastasis. Conclusions. Vasculogenic mimicry is associated with a poor prognosis in patients with gastric cancer in China. Clinical studies with large samples are needed worldwide and standardized protocols should be adopted in the future to achieve a better understanding of the relationship between gastric cancer and vasculogenic mimicry. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of the study? Are CD31+ angiogenic T (TANG) cells preferentially mobilized in response to acute exercise?, What is the main finding and its importance? Our study reveals that TANG cells are redistributed into the circulation in response to acute strenuous exercise, but to a lesser extent than CD31− T cells. Of the TANG cells mobilized, TANG cells expressing CXCR4 show greater redistribution compared with CXCR4− TANG cells. Stromal-derived factor 1-α does not appear to play a role in the redistribution of TANG cells expressing CXCR4. The results suggest that a single bout of strenuous exercise might provide a short vasculogenic window, which could benefit the vascular system by redistributing CD31+ TANG cells., CD31+ T cells have been documented to possess vasculogenic properties and have been termed 'angiogenic T cells' (TANG cells). No study to date has fully characterized the effect of acute exercise on TANG cells. Twelve male participants aged 24-45 years undertook a running 10 km time trial, with peripheral blood samples taken before, immediately after and 1 h postexercise for quantification of TANG cells and subsequent CXCR4 cell surface expression by flow cytometry. The TANG cells demonstrated a 102% increase in number in the peripheral circulation immediately postexercise compared with pre-exercise levels, followed by a large egress (50%) from the circulation in total TANG cells 1 h postexercise. This was due to changes in both CD4+ and CD8+ TANG cells, with CD8+ TANG cells displaying greater ingress (123%) and egress (52%) compared with CD4+ TANG cells (ingress, 83%; egress, 37%). The cell surface expression intensity of CXCR4 was affected only on CD8+ TANG cells, with a significant increase in cell surface expression immediately postexercise versus pre-exercise levels. The CD31− T cells displayed greater redistribution than CD31+ TANG cells (119 versus 102%). CXCR4-expressing TANG cells showed greater response to acute exercise than CXCR4− cells, which was accompanied by large changes in CXCR4 ligand SDF-1α. The results show that acute exercise increases TANG cells in the circulation in response to an acute exercise stressor. Additionally, CXCR4 cell surface expression appears to be increased in response to exercise, which may result from the direct upregulation of CXCR4 on the T-cell surface or could be due to CD31+ T cells being redistributed into the blood expressing greater levels of CXCR4. [ABSTRACT FROM AUTHOR]

Intimate crosstalk occurs between the pulmonary epithelium and the vascular network during lung development. The transcription factor forkhead box f1 ( Foxf1) is expressed in the lung mesenchyme and plays an indispensable role in pulmonary angiogenesis. Sonic hedgehog ( Shh), a signalling molecule, is expressed in lung epithelium and is required to establish proper angiogenesis. It has been suggested that Foxf1, a downstream target of the Shh signalling pathway, mediates interaction between angiogenesis and the epithelium in lung. However, there has been no clear evidence showing the mechanism how Foxf1 is regulated by Shh signalling pathway during lung development. In this study, we investigated the lung-specific enhancers of Foxf1 and the Gli binding on the enhancers. At first, we found three evolutionarily conserved Foxf1 enhancers, two of which were long-range enhancers. Of the long-range enhancers, one demonstrated tissue-specific activity in the proximal and distal pulmonary blood vessels, while the other one demonstrated activity only in distal blood vessels. At analogous positions in human, these long-range enhancers were included in a regulatory region that was reportedly repeatedly deleted in alveolar capillary dysplasia with misalignment of pulmonary vein patients, which indicates the importance of these enhancers in pulmonary blood vessel formation. We also determined that Gli increased the activity of one of these long-range enhancers, which was specific to distal blood vessel, suggesting that Shh regulates Foxf1 transcription in pulmonary distal blood vessel formation. [ABSTRACT FROM AUTHOR]

This research is concerned with microwave ablation analyses using a 2.45 GHz four-tine (4T) antenna for hepatic cancer tissue. In the study, three-dimensional finite-element models were utilized to examine the tissue temperature distributions during and after MW ablation. A preliminary study was first carried out with regard to the specific absorption rates along the 4T antenna insertion depths and the temperature distributions inside the solid and porous liver models with either 3 cm-in-diameter tumor or 5 cm-in-diameter tumor. Based on the preliminary results, the porous models were further examined for the effect of varying blood flow velocities (0–200 cm/s) with a 1 cm-in-diameter blood vessel next to the antenna and also for the effect of vessel-antenna locations (0, 0.8, and 1.3 cm) with a constant blood flow velocity of 16.7 cm/s. All scenarios were simulated under temperature-controlled mode (90°C). The findings revealed that the blood flow velocity and vessel location influence the ablation effectiveness and that increased blood flow inhibits heat transfer to the vessel wall. At the nearest and farthest vessel-antenna locations (0 and 1.3 cm), approximately 90.3% and 99.55% of the cancer cells were eradicated except for the areas adjacent to the vessel. In addition, total tissue thermal displacement is 5.9 mm which is 6.59% of the total length of the overall model. [ABSTRACT FROM AUTHOR]

The method of cardiac magnetic resonance (CMR) three-dimensional (3D) image acquisition and post-processing which should be used to create optimal virtual models for 3D printing has not been studied systematically. Patients ( n = 19) who had undergone CMR including both 3D balanced steady-state free precession (bSSFP) imaging and contrast-enhanced magnetic resonance angiography (MRA) were retrospectively identified. Post-processing for the creation of virtual 3D models involved using both myocardial (MS) and blood pool (BP) segmentation, resulting in four groups: Group 1-bSSFP/MS, Group 2-bSSFP/BP, Group 3-MRA/MS and Group 4-MRA/BP. The models created were assessed by two raters for overall quality (1-poor; 2-good; 3-excellent) and ability to identify predefined vessels (1-5: superior vena cava, inferior vena cava, main pulmonary artery, ascending aorta and at least one pulmonary vein). A total of 76 virtual models were created from 19 patient CMR datasets. The mean overall quality scores for Raters 1/2 were 1.63 ± 0.50/1.26 ± 0.45 for Group 1, 2.12 ± 0.50/2.26 ± 0.73 for Group 2, 1.74 ± 0.56/1.53 ± 0.61 for Group 3 and 2.26 ± 0.65/2.68 ± 0.48 for Group 4. The numbers of identified vessels for Raters 1/2 were 4.11 ± 1.32/4.05 ± 1.31 for Group 1, 4.90 ± 0.46/4.95 ± 0.23 for Group 2, 4.32 ± 1.00/4.47 ± 0.84 for Group 3 and 4.74 ± 0.56/4.63 ± 0.49 for Group 4. Models created using BP segmentation (Groups 2 and 4) received significantly higher ratings than those created using MS for both overall quality and number of vessels visualized ( p < 0.05), regardless of the acquisition technique. There were no significant differences between Groups 1 and 3. The ratings for Raters 1 and 2 had good correlation for overall quality (ICC = 0.63) and excellent correlation for the total number of vessels visualized (ICC = 0.77). The intra-rater reliability was good for Rater A (ICC = 0.65). Three models were successfully printed on desktop 3D printers with good quality and accurate representation of the virtual 3D models. We recommend using BP segmentation with either MRA or bSSFP source datasets to create virtual 3D models for 3D printing. Desktop 3D printers can offer good quality printed models with accurate representation of anatomic detail. [ABSTRACT FROM AUTHOR]

Vegetarian diets have been associated with a lower incidence of several chronic diseases. The benefits of plant-based diets are related mainly to the improvement of metabolic parameters that can indicate risk for such diseases. Some metabolic factors, such as oxidative balance, lipid profile, and glucose homeostasis, can be improved directly by diet, but paradoxically, some characteristics of vegetarian diets may promote a negative scenario that increases the risk of certain chronic diseases. Additionally, many benefits of a vegetarian diet are mediated by the gut microbiota, members of which not only have taxonomic and functional differences but also produce diverse, specific metabolites that vary according to whether the host consumes an omnivorous or a vegetarian diet. This review examines the modulation of human metabolism and gut microbiota by vegetarian and omnivorous dietary patterns and explores how this modulation may affect the risk of cardiovascular disease. [ABSTRACT FROM AUTHOR]

The present study was aimed to evaluate the effect of Teucrium stocksianum on angiogenesis by using chorioallantoic membrane (CAM) assay. Fertilized eggs were incubated on the 5th day and dose of different dilutions 0.03%, 0.05%, 0.1%, and 0.5% of the plant extract was applied on 6th day. Evaluation of primary, secondary and tertiary blood vessels diameter and CAM area on 7th day by SPIP software. T. stocksianum showed anti-angiogenic effect by reducing the diameter of CAM of blood vessels by applying the dilutions while significant results were obtained at dilution of 0.5%. [ABSTRACT FROM AUTHOR]

Key points A consistent inverse hyperbolic relationship has been observed between pulmonary vascular resistance and compliance, although changes in pulmonary artery wedge pressure (PAWP) may modify this relationship., This relationship predicts that pulmonary artery systolic, diastolic and mean pressure maintain a consistent relationship relative to the PAWP., We show that, in healthy exercising human adults, both pulmonary vascular resistance and compliance decrease in relation to exercise-associated increases in PAWP., Pulmonary artery systolic, diastolic and mean pressures maintain a consistent relationship with one another, increasing linearly with increasing PAWP., Increases in PAWP in the setting of exercise are directly related to a decrease in pulmonary vascular compliance, despite small decreases in pulmonary vascular resistance, thereby increasing the pulsatile afterload to the right ventricle., Abstract The resistive and pulsatile components of right ventricular afterload (pulmonary vascular resistance, Rp; compliance, Cp) are related by an inverse hyperbolic function, expressed as their product known as RpCp-time. The RpCp-time exhibits a narrow range, although it may be altered by the pulmonary artery wedge pressure (PAWP). Identifying the determinants of RpCp-time should improve our understanding of the physiological behaviour of pulmonary arterial systolic (PASP), diastolic (PADP) and mean (mPAP) pressures in response to perturbations. We examined the effect of exercise in 28 healthy non-athletic adults (55 ± 6 years) who underwent right heart catheterization to assess haemodynamics and calculate Rp and Cp. Measurements were made at rest and during two consecutive 8-10 min stages of cycle ergometry, at targeted heart-rates of 100 beats min-1 (Light) and 120 beats min-1 (Moderate). Cardiac output increased progressively during exercise. PASP, PADP, mPAP and PAWP increased for Light exercise, without any further rise for Moderate exercise. RpCp-time decreased for Light exercise (0.39 ± 0.08 to 0.25 ± 0.08, P < 0.001) without any further change for Moderate exercise, and the decrease in RpCp-time was related to changes in PAWP ( r2 = 0.26, P < 0.001). Changes in PASP ( r2 = 0.43, P < 0.001), PADP ( r2 = 0.47, P < 0.001) and mPAP ( r2 = 0.50, P < 0.001) were linearly correlated with changes in PAWP, although they were not significantly related to changes in cardiac output. In healthy adults, exercise is associated with decreases in Cp and a resultant decline in RpCp-time, indicating increased pulsatile right ventricular afterload. Changes in RpCp-time, PASP, PADP and mPAP were systematically related to increases in PAWP. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the phytochemical uptake following human consumption of Montmorency tart cherry (L. Prunus cerasus) and influence of selected phenolic acids on vascular smooth muscle cells in vitro. Methods: In a randomised, double-blinded, crossover design, 12 healthy males consumed either 30 or 60 mL of Montmorency tart cherry concentrate. Following analysis of the juice composition, venous blood samples were taken before and 1, 2, 3, 5 and 8 h post-consumption of the beverage. In addition to examining some aspects of the concentrate contents, plasma concentrations of protocatechuic acid (PCA), vanillic acid (VA) and chlorogenic (CHL) acid were analysed by reversed-phase high-performance liquid chromatography (HPLC) with diode array for quantitation and mass spectrometry detection (LCMS) for qualitative purposes. Vascular smooth muscle cell migration and proliferation were also assessed in vitro. Results: Both the 30 and 60 mL doses of Montmorency cherry concentrate contained high amounts of total phenolics (71.37 ± 0.11; 142.73 ± 0.22 mg/L) and total anthocyanins (62.47 ± 0.31; 31.24 ± 0.16 mg/L), as well as large quantities of CHL (0.205 ± 0.24; 0.410 ± 0.48 mg/L) and VA (0.253 ± 0.84; 0.506 ± 1.68 mg/L). HPLC/LCMS identified two dihydroxybenzoic acids (PCA and VA) in plasma following MC concentrate consumption. Both compounds were most abundant 1-2 h post-initial ingestion with traces detectable at 8 h post-ingestion. Cell migration was significantly influenced by the combination of PCA and VA, but not in isolation. There was no effect of the compounds on cell proliferation. Conclusions: These data show new information that phenolic compounds thought to exert vasoactive properties are bioavailable in vivo following MC consumption and subsequently can influence cell behaviour. These data may be useful for the design and interpretation of intervention studies investigating the health effects of Montmorency cherries. [ABSTRACT FROM AUTHOR]

Estrogen receptors, including classic nuclear receptors ER α, ERβ, and membrane receptor GPR30, are expressed in vascular tissues and exert protective actions in vascular diseases. But the expression pattern and functional roles of GPR30 in vascular smooth muscle cells (VSMCs) remain unclear. In this study, we found that ERα, ERβ, and GPR30 were decreased with VSMCs passaging in vitro or growing in vivo and activation of GPR30 promoted ERα expression. Then, we validated that activation of GPR30 significantly decreased migratory capability of VSMCs and suppressed ERα, whereas PDGF-BB (20 ng/mL) treatment caused increase of migration. And activation of GPR30 led to reduction of osteopontin and cellular retinol binding protein 1, enhancement of calponin and 3F8, and upregulation of total and phosphorylated ERK1/2 expression in VSMCs knocked down by GPR30, ERα, and ERβ or treated with PDGF-BB. These data suggest that GPR30 promotes VSMCs reducing migration and maintaining differentiated phenotype via activation of ERK1/2 pathway. Our findings provide novel mechanisms of GPR30 protection of VSMCs as well as a new target for prevention of vascular aging. [ABSTRACT FROM AUTHOR]

The family of nitric oxide synthases (NOS) has significant importance in various physiological mechanisms and is also involved in many pathological processes. Three NOS isoforms have been identified: neuronal NOS (nNOS or NOS 1), endothelial NOS (eNOS or NOS 3), and an inducible NOS (iNOS or NOS 2). Both nNOS and eNOS are constitutively expressed. Classically, eNOS is considered the main isoform involved in the control of the vascular function. However, more recent studies have shown that nNOS is present in the vascular endothelium and importantly contributes to the maintenance of the homeostasis of the cardiovascular system. In physiological conditions, besides nitric oxide (NO), nNOS also produces hydrogen peroxide (H2O2) and superoxide (O2?-) considered as key mediators in non-neuronal cells signaling. This mini-review highlights recent scientific releases on the role of nNOS in vascular homeostasis and cardiovascular disorders such as hypertension and atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Tart cherries contain numerous polyphenolic compounds that could potentially improve endothelial function and reduce cardiovascular disease risk. Objective: We sought to examine the acute effects of Montmorency tart cherry (MC) juice on vascular function in subjects with early hypertension. Design: A placebo-controlled, blinded, crossover, randomized Latin square design study with a washout period of ≥14 d was conducted. Fifteen men with early hypertension [systolic blood pressure (SBP) ≥130 mm Hg, diastolic blood pressure ≥80 mm Hg, or both] received either a 60-mL dose of MC concentrate or placebo. Microvascular reactivity (laser Doppler imaging with iontophoresis), arterial stiffness (pulse wave velocity and analysis), blood pressure, and phenolic acid absorption were assessed at baseline and at 1, 2, 3, 5, and 8 h postconsumption. Results: MC consumption significantly lowered SBP (P < 0.05) over a period of 3 h, with peak reductions of mean ± SEM 7 ± 3 mm Hg 2 h after MC consumption relative to the placebo. Improvements in cardiovascular disease risk factors were closely linked to increases in circulating protocatechuic and vanillic acid at 1-2 h. Conclusions: MC intake acutely reduces SBP in men with early hypertension. These benefits may be mechanistically linked to the actions of circulating phenolic acids. This study provides information on a new application of MCs in health maintenance, particularly in positively modulating SBP. This trial was registered at clinicaltrials.gov as NCT02234648. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to determine the prognostic value of invasively assessing coronary physiology early after heart transplantation.Methods and Results: Seventy-four cardiac transplant recipients had fractional flow reserve, coronary flow reserve, index of microcirculatory resistance (IMR), and intravascular ultrasound performed down the left anterior descending coronary artery soon after (baseline) and 1 year after heart transplantation. The primary end point was the cumulative survival free of death or retransplantation at a mean follow-up of 4.5±3.5 years. The cumulative event-free survival was significantly lower in patients with a fractional flow reserve <0.90 at baseline (42% versus 79%; P=0.01) or an IMR ≥20 measured 1 year after heart transplantation (39% versus 69%; P=0.03). Patients in whom IMR decreased or did not change from baseline to 1 year had higher event-free survival compared with patients with an increase in IMR (66% versus 36%; P=0.03). Fractional flow reserve <0.90 at baseline (hazard ratio, 0.13; 95% confidence interval, 0.02-0.81; P=0.03), IMR ≥20 at 1 year (hazard ratio, 3.93; 95% confidence interval, 1.08-14.27; P=0.04), and rejection during the first year (hazard ratio, 6.00; 95% confidence interval, 1.56-23.09; P=0.009) were independent predictors of death/retransplantation, whereas intravascular ultrasound parameters were not.Conclusions: Invasive measures of coronary physiology (fractional flow reserve and IMR) determined early after heart transplantation are significant predictors of late death or retransplantation. [ABSTRACT FROM AUTHOR]

The lymphatic vasculature is an integral component of the immune system. Lymphatic vessels are a key highway via which immune cells are trafficked, serving not simply as a passive route of transport, but to actively shape and coordinate immune responses. Reciprocally, immune cells provide signals that impact the growth, development, and activity of the lymphatic vasculature. In addition to immune cell trafficking, lymphatic vessels are crucial for fluid homeostasis and lipid absorption. The field of lymphatic vascular research is rapidly expanding, fuelled by rapidly advancing technology that has enabled the manipulation and imaging of lymphatic vessels, together with an increasing recognition of the involvement of lymphatic vessels in a myriad of human pathologies. In this review we provide an overview of the genetic pathways and cellular processes important for development and maturation of the lymphatic vasculature, discuss recent work revealing important roles for the lymphatic vasculature in directing immune cell traffic and coordinating immune responses and highlight the involvement of lymphatic vessels in a range of pathological settings. [ABSTRACT FROM AUTHOR]

Verrucous hemangioma is a rare vascular malformation consisting of a proliferation of dilated blood vessels of different sizes that occupy the dermis and hypodermis. The epidermis of the affected area shows a strong proliferative reaction that presents as a warty appearance. Here, we report the case of a 17-year-old male who presented with an asymptomatic warty growth above the lateral malleolus on the right leg, which healed after electrocautery. [ABSTRACT FROM AUTHOR]

Intense pulsed light (IPL) with low energy insufficient to completely destroy a vasculature was applied to rabbit ears to investigate vasculature alteration. Glycerol was combined with IPL to enhance the transfer efficacy of IPL energy. Both trans-illumination and laser speckle contrast images were obtained and analyzed after treatment. The application of IPL and glycerol combination induced vasodilation and improvement in blood flow. Moreover, such phenomenon was maintained over time. IPL may be applied to treat blood circulatory diseases by inducing vasodilation and to improve blood flow. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic studies have suggested a protective effect of magnesium intake on cardiovascular disease risk. However, intervention trials of magnesium supplementation on blood pressure and conventional cardiometabolic risk markers are inconsistent. Effects on vascular function markers related to cardiovascular disease risk have rarely been studied. Objective: The objective was to evaluate the effects of long-term magnesium supplementation on arterial stiffness. Design: We performed a 24-wk, randomized, double-blind, placebocontrolled intervention study. Fifty-two overweight and slightly obese individuals (30 men and 22 postmenopausal women, mean ± SD age: 62 ± 6 y) were randomly allocated to receive either 3 times daily magnesium (3 × 117 mg or 350 mg/d) or placebo capsules. Twenty-four-hour urine collections and 24-h ambulatory blood pressure assessments were performed at the start and end of the study. Carotid-to-femoral pulse wave velocity (PWVc-f) was assessed at baseline, after 12 wk, and at week 24. Results: Serum magnesium concentrations did not differ after 12 wk but tended to increase after 24-wk magnesium supplementation compared with placebo by 0.02 mmol/L (95% CI: 0.00, 0.04 mmol/L; P = 0.09). Twenty-four-hour urinary magnesium excretion increased by 2.01 mmol (95% CI: 1.22, 2.93 mmol; P < 0.001) at week 24. PWVc-f was not changed after 12 wk (0.0 m/s; 95% CI: –0.6, 0.5 m/s; P = 0.90) but was improved in the magnesium compared with the placebo group by 1.0 m/s (95% CI: 0.4, 1.6 m/s; P = 0.001) after 24 wk. Office and 24-h ambulatory blood pressure levels were not changed. No adverse events were observed. Conclusion: Our data indicate that a daily magnesium supplement of 350 mg for 24 wk in overweight and obese adults reduces arterial stiffness, as estimated by a decrease in PWVc-f, suggesting a potential mechanism by which an increased dietary magnesium intake beneficially affects cardiovascular health. This trial was registered at clinicaltrials.gov as NCT02235805. [ABSTRACT FROM AUTHOR]

Background: In the rat model of high carbohydrate, high fat (HCHF) diet-induced metabolic syndrome (MS), previous studies have found that asiatic acid has an antihypertensive effect. In this study, we investigated effects of asiatic acid on vascular structure, vascular function and renin-angiotensin system (RAS) in HCHF diet-induced MS rats. Methods: Male Sprague-Dawley rats were divided into three treatment groups for the 15 week study: a control group fed a normal diet, a MS group fed HCHF diet plus 15 % fructose in their drinking water for 15 weeks, and an asiatic acid treated group that received a HCHF diet plus fructose for 15 weeks and also received orally administered asiatic acid (20 mg/kg BW/day) for the final 3 weeks. Vascular structure and function were investigated. AT1 receptor expression in aortic tissues and eNOS protein expression in the mesenteric arteries were detected. The levels of serum angiotensin (Ang) II, angiotensin converting enzyme (ACE) and plasma norepinephrine (NE) were measured. The differences among treatment groups were analyzed by one-way analysis of variance (ANOVA) followed by post-hoc Bonferroni tests. Results: At the end of the study, all rats fed a HCHF diet exhibited signs of MS including, hypertension, dyslipidemia and insulin resistance. Vascular remodeling in large and small arteries, overexpression of AT1 receptor, and high levels of serum Ang II and ACE were also observed in MS group (p < 0.05). Contractile responses to sympathetic nerve stimulation were enhanced relating to high plasma NE level in MS rats (p < 0.05). The response to exogenous NE was not changed in the mesenteric bed. Vasorelaxation responses to acetylcholine were blunted in thoracic aorta and mesenteric beds, which is consistent with downregulation of eNOS expression in MS rats (p < 0.05). Restoration of metabolic alterations, hemodynamic changes, RAS and sympathetic overactivity, increased plasma NE, endothelium dysfunction, and downregulation of eNOS expression was observed in the asiatic acid treated group (p < 0.05). However, asiatic acid failed to alleviate vascular remodeling in MS rats. Conclusion: Our findings suggest that the observed antihypertensive effect of asiatic acid in MS rats might be related to its ability to alleviate RAS overactivity and improve vascular function with restoration of sympathetic overactivity. [ABSTRACT FROM AUTHOR]

In the process of leukocyte migration from the circulation across the vascular wall, the crosstalk with endothelial cells that line the blood vessels is essential. It is now firmly established that in endothelial cells important signaling events are initiated upon leukocyte adhesion that impinge on the regulation of cell-cell contact and control the efficiency of transendothelial migration. In addition, several external factors such as shear force and vascular stiffness were recently identified as important regulators of endothelial signaling and, consequently, leukocyte transmigration. Here, I review recent insights into endothelial signaling events that are linked to leukocyte migration across the vessel wall. In this field, protein phosphorylation and Rho-mediated cytoskeletal dynamics are still widely studied using increasingly sophisticated mouse models. In addition, activation of tyrosine phosphatases, changes in endothelial cell stiffness as well as different vascular beds have all been established as important factors in endothelial signaling and leukocyte transmigration. Finally, I address less-well-studied but interesting components in the endothelium that also control transendothelial migration, such as the ephrins and their Eph receptors, that provide novel insights in the complexity associated with this process. [ABSTRACT FROM AUTHOR]

Background: The emergence and development of robot assistant interventional vascular surgery technologies have benefited many patients with cardiovascular or cerebrovascular diseases. Due to the absence of effective training measures, these new advanced technologies have not been fully utilized and only few experienced surgeons can perform such complicated surgeries so far. In order to solve such problems, virtual reality based vascular interventional surgery training system, a promising way to train young surgeons or assist experienced surgeons to perform surgery, has been widely studied.Methods: In this paper, we mainly conduct a thorough study on both reliable deformation and high real-time performance of an interactive surgery training system. An efficient hybrid geometric blood vessel model which handles the collision detection query and vascular deformation calculation separately is employed to enhance the real-time performance of our surgery training system. In addition, a position-based dynamic approach with volume conservation constraint is used to improve the vascular deformation result. Finally, a hash table based spatial adaptive acceleration algorithm which makes the training system much more efficient and reliable is described.Results: Several necessary experiments are conducted to validate the vascular deformation scheme presented in this paper. From the results we can see that the position-based dynamic modeling method with volume conservation constraint can prevent the vascular deformation from the issue of penetration. In addition, the deformation calculation with spatial acceleration algorithm has enhanced the real-time performance significantly.Conclusion: The corresponding experimental results indicate that both the hybrid geometric blood vessel model and the hash table based spatial adaptive acceleration algorithm can enhance the performance of our surgery training system greatly without losing the deformation accuracy. [ABSTRACT FROM AUTHOR]

Background: The shape of human red blood cells (RBCs) deteriorates progressively throughout hypothermic storage, with echinocytosis being the most prevalent pathway of this morphologic lesion. As a result, each unit of stored blood contains a heterogeneous mixture of cells in various stages of echinocytosis and normal discocytes. Here we studied how the change in shape of RBCs following along the path of the echinocytic transformation affects perfusion of an artificial microvascular network (AMVN).Study Design and Methods: Blood samples were obtained from healthy consenting volunteers. RBCs were leukoreduced, resuspended in saline, and treated with various concentrations of sodium salicylate to induce shape changes approximating the stages of echinocytosis experienced by RBCs during hypothermic storage (e.g., discocyte, echinocyte I, echinocyte II, echinocyte III, spheroechinocyte, and spherocyte). The AMVN perfusion rate was measured for 40% hematocrit suspensions of RBCs with different shapes.Results: The AMVN perfusion rates for RBCs with discocyte and echinocyte I shapes were similar, but there was a significant decline in the AMVN perfusion rate between RBCs with shapes approximating each subsequent stage of echinocytosis. The difference in AMVN perfusion between discocytes and spherocytes (the last stage of the echinocytic transformation) was 34%.Conclusion: The change in shape of RBCs from normal discocytes progressively through various stages of echinocytosis to spherocytes produced a substantial decline in the ability of these cells to perfuse an AMVN. Echinocytosis induced by hypothermic storage could therefore be responsible for a similarly substantial impairment of deformability previously observed for stored RBCs. [ABSTRACT FROM AUTHOR]

Tumor blood vessels provide nutrition and oxygen to the tumor, resulting in tumor progression. They also act as gatekeepers, inducing tumor metastasis. Thus, targeting tumor blood vessels is an important strategy in cancer therapy. Tumor endothelial cells (TECs), which line the inner layer of blood vessels of the tumor stromal tissue, are the main targets of anti-angiogenic therapy. Because new tumor blood vessels generally sprout from pre-existing vasculature, they have been considered to be the same as normal blood vessels. However, tumor blood vessels demonstrate a markedly abnormal phenotype that includes several important morphological changes. The degree of angiogenesis is determined by the balance between the angiogenic stimulators and inhibitors released by the tumor and host cells. Recent studies have revealed that TECs also exhibit altered characteristics which depend on the tumor microenvironment. Here, we review recent studies on TEC abnormalities and heterogeneity with respect to tumor progression and consider their therapeutic implications. [ABSTRACT FROM AUTHOR]

Thermo-responsive shape memory polymers (SMPs) can be programmed to fit into small-bore incisions and recover their functional shape upon deployment in the body. This property is of significant interest for developing the next generation of minimally-invasive medical devices. To be used in such applications, SMPs should exhibit adequate mechanical strengths that minimize adverse compliance mismatch-induced host responses (e.g. thrombosis, hyperplasia), be biodegradable, and demonstrate switch-like shape recovery near body temperature with favorable biocompatibility. Combinatorial approaches are essential in optimizing SMP material properties for a particular application. In this study, a new class of thermo-responsive SMPs with pendant, photocrosslinkable allyl groups, x %poly(ε-caprolactone)-co- y %(α-allyl carboxylate ε-caprolactone) ( x %PCL- y %ACPCL), are created in a robust, facile manner with readily tunable material properties. Thermomechanical and shape memory properties can be drastically altered through subtle changes in allyl composition. Molecular weight and gel content can also be altered in this combinatorial format to fine-tune material properties. Materials exhibit highly elastic, switch-like shape recovery near 37 °C. Endothelial compatibility is comparable to tissue culture polystyrene (TCPS) and 100%PCL in vitro and vascular compatibility is demonstrated in vivo in a murine model of hindlimb ischemia, indicating promising suitability for vascular applications. Statement of Significance With the ongoing thrust to make surgeries minimally-invasive, it is prudent to develop new biomaterials that are highly compatible and effective in this workflow. Thermo-responsive shape memory polymers (SMPs) have great potential for minimally-invasive applications because SMP medical devices (e.g. stents, grafts) can fit into small-bore minimally-invasive surgical devices and recover their functional shape when deployed in the body. To realize their potential, it is imperative to devise combinatorial approaches that enable optimization of mechanical, SM, and cellular responses for a particular application. In this study, a new class of thermo-responsive SMPs is created in a robust, facile manner with readily tunable material properties. Materials exhibit excellent, switch-like shape recovery near body temperature and promising biocompatibility for minimally-invasive vascular applications. [ABSTRACT FROM AUTHOR]

Rhipicephalus microplus is an ectoparasite responsible for transmissions of babesiosis and anaplasmosis causing large losses to livestock production. To survive R. microplus tick produces several active molecules, such as protease inhibitors. This ectoparasite has been described as a rich source of serine protease inhibitors most of them are Kunitz-BPTI members named BmTIs which have no clear function yet. In the present work, we described the expression and functional characterization of rBmTI-A which showed to be similar to the native BmTI-A, a double-headed Kunitz-BPTI inhibitor, capable to inhibit trypsin, human neutrophil elastase (HNE), human plasma kalikrein (HuPK) and human plasmin. rBmTI-A was able to cause a decrease of HUVEC cell viability. Besides, the rBmTI-A showed to be a potent inhibitor of “in vitro” vessel formation. Our results suggested that BmTI-A may participate in the blood acquisition process interfering in the vessel formation during the tick parasite life stage, around 20 days. In conclusion, BmTI-A is a promising molecule to be used in the drug design and development of new method of R. microplus control. [ABSTRACT FROM AUTHOR]

Previous studies have shown that hemostatic thrombi formed in response to penetrating injuries have a core of densely packed, fibrin-associated platelets overlaid by a shell of less-activated, loosely packed platelets. Here we asked, first, how the diverse elements of this structure combine to stem the loss of plasma-borne molecules and, second, whether antiplatelet agents and anticoagulants that perturb thrombus structure affect the reestablishment of a tight vascular seal. The studies combined high-resolution intravital microscopy with a photo-activatable fluorescent albumin marker to simultaneously track thrombus formation and protein transport following injuries to mouse cremaster muscle venules. The results show that protein loss persists after red cell loss has ceased. Blocking platelet deposition with an α IIbβ3 antagonist delays vessel sealing and increases extravascular protein accumulation, as does either inhibiting adenosine 5'-diphosphate (ADP) P2Y12 receptors or reducing integrin-dependent signaling and retraction. In contrast, sealing was unaffected by introducing hirudin to block fibrin accumulation or a Gi2a gain-of-function mutation to expand the thrombus shell. Collectively, these observations describe a novel approach for studying vessel sealing after injury in real time in vivo and show that (1) the core/shell architecture previously observed in arterioles also occurs in venules, (2) plasma leakage persists well beyond red cell escape and mature thrombus formation, (3) the most critical events for limiting plasma extravasation are the stable accumulation of platelets, ADP-dependent signaling, and the emergence of a densely packed core, not the accumulation of fibrin, and (4) drugs that affect platelet accumulation and packing can delay vessel sealing, permitting protein escape to continue. [ABSTRACT FROM AUTHOR]