bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of Cyclooxygenase‐2 Following Anoxic Stress in Piglet Cerebral Arteries
Authors: Busija David W. , Thore Clara , Beasley Tracy , Bari Ferenc 
Published: April 2008

ABSTRACT Objective: Ischemic stress causes damage to cerebrovascular endothelium and alters arteriolar responses to prostanoid‐dependent stimuli. However, effects of ischemic stress on cyclooxygenase (COX) levels in endothelium are unclear. We examined the effect of ischemia and reperfusion and asphyxia and reventilation on production of COX isoforms in cerebral vascular endothelium. Methods: Neonatal pigs were exposed to global ischemia (n= 4) or asphyxia (n= 3) for 5–10 min. Following 2–6 h of recovery, the animals were killed, and the cerebral arteries and arterioles were removed. Cerebral arteries and arterioles were also removed from untreated control animals (n= 1) and from time control animals (n= 3). Cerebral vessels were fixed in 4% formalin and paraffin embedded, and constitutive and inducible COX (COX‐1 and COX‐2, respectively) levels were assessed using indirect immunofluorescence. Results: Hemotoxylin and eosin staining indicated that anoxic stress leads to enlargement of endothelial cells. Immunofluorescence for COX‐1 in endothelium was minimal in cerebral arteries and arterioles from control animals and did not show an increase in animals exposed to anoxic stress. Similarly, cerebral vessels from control animals showed little immunostaining for COX‐2. In contrast, immunofluorescence for COX‐2 was greatly increased in cerebral arteries and arterioles from animals exposed to asphyxia or ischemia. Conclusions: We conclude that anoxic stress increases COX‐2 but not COX‐1 levels in cerebral endothelium.
Oxidative Stress During Platelet‐Activating Factor‐Induced Microvascular Dysfunction
Authors: Kurose Iwao , Argenbright Lawrence W. , Wolf Robert , Granger D. Neil 
Published: April 2008

ABSTRACT Objective: To assess the potential contribution of hydrogen peroxide (H2O2) to the leukocyte‐endothelial cell adhesion and increased microvascular permeability (to fluorescein isothiocyanate [FITC]‐albumin) observed in rat mesenteric venules exposed to platelet‐activating factor (PAF). Methods: The production of oxidants derived from H2O2 in mesenteric tissue was monitored using the H2O2‐sensitive fluorochrome, dihydrorhodamine 123 (DHR). PAF elicited a rapid increase in both the rate of albumin extravasation and oxidation of DHR, which was followed by an increased adherence and emigration of leukocytes in postcapillary venules. Results: The PAF‐induced oxidation of DHR, leukocyte‐endothelial cell interactions, and albumin leakage were attenuated by treatment with either catalase or dimethylthiourea. Treatment with monoclonal antibody directed against either CD11b/CD18 on leukocytes or ICAM‐1 on endothelial cells attenuated the PAF‐induced oxidative stress, albumin leakage, and leukocyte‐endothelial cell adhesion. Conclusions: These findings indicate that most of the oxidants generated in mesenteric tissue exposed to PAF results from the accumulation of activated leukocytes.
Remodeling of Capillary Network in Left Ventricular Subendocardial Tissues Induced by Intravenous Vasopressin Administration
Authors: Xie Zhonglin , Gao Ming , Batra Sanjay , Koyama Tomiyasu 
Published: April 2008

ABSTRACTObjective: The question of whether the coronary vasospasm induced by intravenous administration of vasopressin produces any remodeling of the capillary network in the left ventricle was investigated. To this end, cardiac tissues obtained from vasopressin‐injected rats were stained to allow capillary counting and for basic fibroblast growth factor (bFGF).Methods: Nine male Donryu rats were divided into three groups that received, respectively, 0.25 ml of saline containing 0, 0.5, or 1.0 U/kg vasopressin injected into the tail vein once daily for 4 days. Rats were killed 30 days after the last injection. Two additional rats each received a single intravenous injection of 1.0 U/kg vasopressin and were killed 24 hours later. The left ventricles were removed and 16‐ or 10‐μm frozen sections were cut for differential staining and distribution of bFGF, respectively. Differential staining was used to classify the capillary portions, and bFGF was identified by immunohistological staining.Results: Compared with the control group, total capillary density was increased in both vasopressin‐treated groups, capillary to myocyte ratio was increased, and the capillary domain areas decreased in the three capillary portions. Arteriolar and intermediate capillary portions increased, while the venular capillary portion decreased. In rats killed 24 hours after vasopressin injection, a considerable amount of bFGF could be demonstrated immunohistochemically in the ventricular tissues, and the punctate distribution of bFGF was still found in rats killed 30 days after treatment.Conclusions: A remodeling of capillary network which would increase the oxygen transport capacity to cardiac tissues was produced in left ventricular tissues by intravenous injection of vasopressin. bFGF located around capillaries and in the interstitial space may have been involved in the capillary remodeling.
Vascular Endothelial Cadherin (VE‐Cadherin): Cloning and Role in Endothelial Cell‐Cell Adhesion
Authors: Ali Jahanara , Liao Fang , Martens Eric , Muller William A. 
Published: April 2008

ABSTRACTObjective: To identify proteins responsible for intercellular junction integrity in human umbilical vein endothelial cells (HUVEC), we produced a monoclonal antibody that recognized an endothelial cell‐specific, junctionally restricted protein. We characterized and cloned the antigen to study its functional properties.Methods: The size and cellular distribution of the antigen were determined by immunofluorescence and immunoprecipitation. The molecule was cloned and transfected into cell lines, and its role in cell‐cell adhesion and growth rate was determined.Results: Monoclonal antibody heel recognizes VE‐cadherin, an endothelial cell‐restricted cell adhesion molecule. VE‐cadherin is localized to the borders between apposing endothelial cells but is diffusely distributed on subconfluent or migrating cells. Transfection of fibroblasts with VE‐cadherin imparts to them the ability to adhere to each other in a calcium‐dependent homophilic manner. Expression of VE‐cadherin over a several‐log range does not change the growth rate of these cells.Conclusions: Despite the fact that VE‐cadherin is a “nonclassical” cadherin by structure, it functions as a classic cadherin by imparting to cells the ability to adhere in a calcium‐dependent, homophilic manner. On HUVEC it appears to play a role in maintaining monolayer integrity.
Shear Rate Dependency of Red Cell Sequestration in Skin Capillaries in Sickle Cell Disease and Its Variation with Vasoocclusive Crisis
Authors: Lipowsky Herbert H. , Williams Melanie E. 
Published: April 2008

ABSTRACTObjective: To develop techniques for assessing the sequestration of red blood cells (RBCs) in skin capillaries of sickle cell disease (SCD) patients due to RBC adhesion to endothelium (EC) and RBC aggregation, and to determine the extent to which these processes correlate with onset of painful vasoocclusive crisis.Methods: Video recordings of nailfold capillaries in the skin of patients with SCD were made during steady‐state periods and episodes of painful crisis. A transient low‐flow state was induced with a pressure cuff, and reductions in RBC velocity were measured by spatial cross‐correlation of light intensity along arterial and venous capillary limbs. An RBC accumulation index (AI) was calculated from RBC flow to represent the percentage of arterial in‐flow sequestered in a capillary. An index of hematocrit (HI) was derived from axial distributions of light intensity, and a sequestration index (SI) was calculated to represent the relative increase of venous limb HI relative to that in the arterial limb with onset of stasis.Results: Both AI and SI increased dramatically from zero at steady flow to a maximum as shear rates within the capillary were reduced to zero. The increase was small until shear rates (γ) fell below a transition value (γT), following which both AI and SI increased sharply with onset of stasis. For 20 ≤ γ < γT the transient increase in AI was significantly elevated in the order AICRISIS > AISTEADY STATE > AICONTROL, thus reflecting increasing RBC sequestration in the venous limb due to either adhesion or aggregation. Compaction of RBCs in the venous limb was evidenced by increased SI that was greater than control for both steady‐state and crisis subjects, but insignificantly elevated during crisis compared to steady state, thus supporting a lesser role of RBC aggregation.Conclusions: Transient sequestration of sickle RBCs in the low‐flow state appears to be dominated by RBC‐EC adhesion, which becomes enhanced during crisis. Although aggregation may enhance adhesive contact of RBCs with EC, it does not increase to the same extent as the rate of sequestration, thus reflecting a greater role of RBC‐EC adhesion.
The Cutaneous Microcirculation: Ultrastructure and Microanatomical Organization
Authors: Braverman Irwin M. 
Published: April 2008

ABSTRACTThe cutaneous microcirculation is organized as two horizontal plexuses. One is situated 1–1.5 mm below the skin surface, and the other is at the dermal‐subcutaneous junction. Ascending arterioles and descending venules are paired as they connect the two plexuses. From the upper layer, arterial capillaries arise to form the dermal papillary loops that represent the nutritive component of the skin circulation. There are sphincter‐like smooth muscle cells at the point where the ascending arterioles divide to form the arteriolar component of the upper horizontal plexus. At the dermal subcutaneous junction, there are collecting veins with 2‐cusped valves that are oriented to prevent the retrograde flow of blood. Laser Doppler flowmetry (LDF) has demonstrated vasomotion of red cell flux localized to the sites of ascending arterioles. The simultaneous recording by LDF of red cell flux and the concentration of moving red blood cells from individual sites allows one to construct by computer topographic maps of these two valves. The two maps, based on initial studies using correlative skin biopsy specimens, can define 1‐mm3 volumes of skin that are predominantly arteriolar in composition, predominantly venular in composition, or essentially devoid of all microvascular elements. The electron and light microscopic features that define the microvascular segments, when coupled with the ability of LDF to define the predominant microvascular segments under the probe, will allow one to study both the mechanisms of normal physiological states and the pathogenetic mechanisms underlying pathological skin disorders in which the microvasculature plays a predominant role.
Redox Control of Ion Channel Activity in Vascular Endothelial Cells by Glutathione
Authors: Elliott Stephen J. , Koliwad Suneil K. 
Published: April 2008

ABSTRACTOxidized glutathione (GSSG) is endogenously formed within vascular endothelial cells. The bioactivity of GSSG results in the oxidation of protein thiol groups, leading to changes in protein structure‐function relationships. When ion channel protein thiols are the target of oxidation by GSSG, important changes in channel conductance, activity, and gating occur. In this review, we focus on two endothelial cell ion channels, the activities of which influence vascular cell signaling and the nitric oxide signaling pathway. The first channel is the GSSG‐operated cation channel that depolarizes the endothelial cell, leading to inhibition of capacitative Ca2+ entry. The second channel is the inositol 1,4,5‐triphosphate (IP3)‐operated Ca2+ channel that is responsible for the agonist‐stimulated release of Ca2+ from IP3‐sensitive endoplasmic reticulum. GSSG acts to deplete IP3‐sensitive Ca2+ stores, thereby attenuating the intracellular Ca2+ response to agonist stimulation. Together, these effects indicate that glutathione, which is formed endogenously within the cell, is a key physiological modulator of endothelial cell signaling.
Lung Neutrophil Retention and Injury After Intestinal Ischemia/Reperfusion
Authors: Xiao Feng , Eppihimer Michael J. , Young Jay A. , Nguyen Khoa , Carden Donna L. 
Published: April 2008

ABSTRACTObjective: To define the mechanisms responsible for the lung leukosequestration and injury elicited by intestinal ischemia/reperfusion (I/R).Methods: The effect of 120 minutes of superior mesenteric artery occlusion and 90 minutes of reperfusion on neutrophil deformability, lung neutrophil retention, and pulmonary microvascular permeability was determined.Results: Compared with control surgery, intestinal I/R resulted in a significant increase in neutrophil stiffness (mean yield pressure [Pyieid], 1–533 ± 0.075 and 2.302 ± 0.288 cm H2O, respectively) and lung neutrophil content (6.3 ± 1.4 and 31.5 ± 6.4 U/g wet weight, respectively). These changes were not affected by inhibition of neutrophil adherence before gut reperfusion. However, the increased lung microvascular permeability elicited by gut I/R (0.111 ± 0.020 [control surgery] and 0.255 ± 0.041 [I/R] mL/min/cm H2O/100 g lung tissue) was significantly attenuated by administration of antibodies directed against neutrophil or endothelial determinants of leukocyte adhesion.Conclusions: The results of this study suggest that intestinal I/R is a potent inflammatory stimulus that elicits an increase in neutrophil stiffness and lung neutrophil retention independent of neutrophil‐endothelial cell adhesion. In contrast, the increased lung microvascular permeability elicited by gut I/R is attenuated by strategies that interfere with neutrophil‐endothelial cell adhesion.
Myogenic Responses of Isolated Lymphatics: Modulation by Endothelium
Authors: Mizuno Risuke , Dörnyei Gabriella , Koller Akos , Kaley Gabor 
Published: April 2008

ABSTRACTObjective: To characterize the effect of increases of intraluminal pressure on the spontaneous diameter oscillations of isolated lymphatics and on the maximum and minimum diameter, in the presence and absence of endothelium.Methods: Afferent lymphatics were isolated from rat iliac lymph nodes. After cannulation of both ends, lymphatics were equilibrated for 60 minutes at a pressure of 6 cm H2O, and then changes in diameter oscillations to increases in perfusion pressure (from 2–10 cm H2O) were measured. The endothelium was removed by intraluminal infusion of air. Changes in diameter were expressed as a percentage of the corresponding passive diameter obtained in Ca2+‐free solution.Results: Isolated lymphatics showed phasic spontaneous constriction and dilation (∼50 to ∼150 μm). Removal of extracellular Ca2+ abolished spontaneous diameter oscillations, and the passive diameter increased from 183.0 ± 5.3 to 205.1 ± 8.8 μm as pressure increased from 2 to 10 cm H2O. In response to increases in pressure, the normalized minimum diameter (Dmin) increased (from 30.1% ± 1.1% to 54.8% ± 1.9%) while the normalized maximum diameter (Dmax) of lymphatics did not change. With increasing pressure the amplitude of vasomotion (Dmax‐Dmin) decreased, whereas the oscillation frequency increased. Removal of endothelium significantly reduced Dmax; hence, the oscillation amplitude decreased while the frequency increased. Also, endothelium removal elicited a significant change in the slope of the pressure‐Dmax curve (from 0.01 ± 0.4 to −1.43 ± 0.34).Conclusions: Increases in intraluminal pressure greatly affect the spontaneous vasomotion of lymphatics and activate the myogenic mechanism intrinsic to the smooth muscle. In addition, endothelial factors are important to maintain adequate lymphatic vasomotion. These findings suggest that intraluminal pressure and endothelial factors can be important contributors to the tone and pumping activity of lymphatics in vivo.
Mechanical Remodeling of the Endothelial Surface and Actin Cytoskeleton Induced by Fluid Flow
Authors: Satcher Robert , Dewey C. Forbes , Hartwig John H. 
Published: April 2008

ABSTRACTObjective: The mechanism by which cultured endothelial cells respond to shear stress is controversial. The cell surface and cytoskeleton are involved, but their roles are undefined. In this study, previously unknown changes in the surface detail and actin cytoskeleton of bovine aortic endothelial cells were identified.Methods: Actin filament content and filament number in resting and flow‐oriented cells were determined by biochemical assays. The three‐dimensional organization of the actin cytoskeleton in cells was defined in the confocal microscope and in the electron microscope after rapid‐freezing, freeze‐drying, and metal coating of detergent‐permeabilized cells.Results: Endothelial cells have smooth apical membranes in situ. However, cultured cells exhibit surface microvilli which increase the apical surface area, exposing the ruffled surface to forces from fluid flow and potentially enhancing cell interactions with blood‐borne white cells. Stereoscopic micrographs show that stress fibers are integrated into a complex distributed cytoplasmic structural actin network (DCSA). This lattice is formed by actin filaments that frequently cross and connect to each other, stress fibers, and microfilaments and microtubules. The cytoskeletons of cells cultured in static media lack apparent order when compared to cytoskeletons from cells which have been exposed to 24 hours of laminar flow.Conclusions: The DCSA physically connects the apical and basal cell membranes and fills the volume between nucleus and membrane, providing a mechanism for transmitting mechanical forces across cells and a signaling pathway from membrane to nucleus. Stress fibers increase the mechanical modulus of the DCSA, although this increase is probably unnecessary to withstand the increase in shear stress caused by blood flow in vivo. This implies that actin rearrangements are not required for mechanical integrity, but serve an alternate function.
A Semiautomatic Procedure for Edge Detection of In Vivo Pulmonary Microvessels and Interstitial Space
Authors: Crisafulli Beatrice , Boschetti Federica , Venturoli Daniele , Del Fabbro Massimo , Miserocchi Giuseppe 
Published: April 2008

ABSTRACTObjective: To develop an algorithm to detect the edges between lung tissue, perivascular interstitium. and microvessel using digital processing of in vivo microscopic images of lung surface.Methods: A numerical technique was developed to identify three different regions (namely, pulmonary microvessel, perivascular interstitium, and lung tissue) based on their corresponding gray level distributions. We present a theoretical demonstration of the method and a semiautomatic procedure that, once the edges are detected, determines microvascular diameters and perivascular interstitium thickness.Results: Microvessel diameters and perivascular interstitium thickness were calculated for precapillary arteriolar branching (40 to 140 μm) and saved in an ASCII file.Conclusions: We proved that the maximum value of the moving variance is useful to detect the edge between two adjacent regions whose gray level distributions satisfy the condition: ∥σY2‐σX2∥ ≤ (μX‐μY)2, where μX, μY, σX2, σY2 are the statistical moments of the two regions X and Y. Moreover, when the regions have similar means, the above condition is not met, but the edge between them can be detected by the maximum of the moving variance error.
Geometric Resistance and Microvascular Network Architecture of Human Colorectal Carcinoma
Authors: Less Joanne R. , Posner Mitchel C. , Skalak Thomas C. , Wolmark Norman , Jain Rakesh K. 
Published: April 2008

ABSTRACTObjective: To measure the geometric resistance to blood flow in human colorectal carcinoma. Although tumor blood flow is of central importance in both the detection and the treatment of cancer, the determinants of blood flow through the neoplastic circulation are poorly understood.Methods: Human colorectal carcinomas (tissue weight = 272 g ± 43 g (SD), n = 6) were perfused ex vivo with a buffered physiological salt solution of known viscosity at flow rates ranging from 2.5 to 40 ml/min and perfusion pressures from 8 to 100 mm Hg. The geometric resistance was determined from the slope of the pressure‐flow curve. For examination of the principal determinant of geometric resistance, the vascular architecture, one of the tumors was perfused with Batson's No. 17 polymer and macerated in KOH to produce a positive vascular cast that was used for measurement of vascular branching patterns and dimensions.Results: The pressure‐flow relationship was linear at perfusion pressures above 40 mm Hg, and the geometric resistance, z0, was constant at approximately 6.5 ± 109g/cm3. Below 40 mm Hg, z0 increased rapidly. The architecture of the arteriolar and capillary networks of human colorectal carcinoma is similar to those of experimental rodent tumors. Capillaries in planar and nonplanar mesh‐works had mean segment diameters of 11 ± 2 and 9.6 ± 2 μm, lengths of 46 ± 24 and 107 ± 40 μm, and intercapillary distances of 46 ± 13 and 74 ± 24 μm, respectively.Conclusions: The geometric flow resistance in neoplastic tissue is 1–2 orders of magnitude higher than that observed in normal tissues. A decrease in functional vascular cross‐sectional area may explain the additional increase in resistance at small perfusion pressures. The observed flow resistance may be due to the specialized arteriolar and capillary network architecture, pressures exerted by proliferating cancer cells, and/or coupling between vascular and extravascular flow. These observations demonstrate that tumor vascularity alone may not be indicative of flow resistance or tumor susceptibility to blood‐borne therapeutic agents.