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At least 145 records · Page 8Linked to original sources
PubMed2005

Histidine-rich glycoprotein: A novel adaptor protein in plasma that modulates the immune, vascular and coagulation systems.

Histidine-rich glycoprotein (HRG) is an abundant plasma glycoprotein that has a multidomain structure, interacts with many ligands, and has been shown to regulate a number of important biological processes. HRG ligands include Zn(2+) and haem, tropomyosin, heparin and heparan sulphate, plasminogen, plasmin, fibrinogen, thrombospondin, IgG, FcgammaR and complement. In many cases, the histidine-rich region of the molecule enhances ligand binding following interaction with Zn(2+) or exposure to low pH, conditions associated with sites of tissue injury or tumour growth. The multidomain nature of HRG indicates that it can act as an extracellular adaptor protein, bringing together disparate ligands, particularly on cell surfaces. HRG binds to most cells primarily via heparan sulphate proteoglycans, binding which is also potentiated by elevated free Zn(2+) levels and low pH. Recent reports have shown that HRG can modulate angiogenesis and additional studies have shown that it may regulate other physiological processes such as cell adhesion and migration, fibrinolysis and coagulation, complement activation, immune complex clearance and phagocytosis of apoptotic cells. This review outlines the molecular, structural, biological and clinical properties of HRG as well as describing the role of HRG in various physiological processes.

Animals↗
PubMed2000

Adaptation of post-traumatic angiogenesis in the rabbit knee by apposition of torn ligament ends.

Apposition of torn ligament ends has been shown to have a beneficial effect on healing of the medial collateral ligament; however, the mechanism underlying this improved recovery is unclear. Excessive post-traumatic angiogenesis, an inherent component of soft-tissue regeneration, may be functionally detrimental in relatively hypovascular tissues such as ligaments. The present study therefore examined the relationship between contact of transected ligament ends and vascular remodeling. Female New Zealand White rabbits were subjected to a gap injury, Z-plasty apposition, or sham operation to the midsubstance of the medial collateral ligament. Six weeks after treatment, the volume of vessels supplying the healing zone of the medial collateral ligament, as well as the ipsilateral lateral collateral ligament, posterior cruciate ligament. menisci, and medial capsule, was quantified by carmine red vascular casting. The volume of vessels supplying the neoligamentous scar formed by gap injury to the medial collateral ligament was found to be twice that of ligaments that had undergone the sham operation, and lateral collateral ligament and meniscal vascularity was also augmented in the injured joint. The medial collateral ligaments that underwent Z-plasty apposition exhibited a level of vascularity comparable with that of the control ligaments that had undergone the sham procedure, whereas meniscal and lateral collateral ligament vascularities remained elevated in this group. Capsular and posterior cruciate ligament vascularities were unaffected by gap injury or Z-plasty to the ipsilateral medial collateral ligament. These findings indicate that injury to the medial collateral ligament not only stimulates angiogenesis in the healing ligament, but other ipsilateral soft tissues also undergo vascular remodeling. Furthermore, apposition of an injured medial collateral ligament modifies these pro-angiogenic events, and this may partly explain why contact of torn ligament ends is beneficial for post-traumatic recovery of an injured joint.

Adaptation, Physiological↗
PubMed2004

Endocrine and paracrine control of follicular development and ovulation rate in farm species.

Productivity in farm species is controlled by many factors, including ovulation rate. In cattle, single ovulations occur most frequently and in sheep (and goats) the number of ova released can range from one to many depending upon the breed, whilst the pig is polyovular. The processes of recruitment and selection determine the number of ovulatory follicles in all these species with FSH and subsequently LH playing major roles. GnRH-agonist models in which endogenous gonadotrophin secretion is suppressed and exogenous LH and/or FSH are administered at specific concentrations in defined patterns, are useful in all three species for elucidating the precise roles of specific hormones in stimulating follicular development. Differences in the hypothalamic-pituitary-ovarian feedback response lead to the differences in the number of ovulatory follicles, as does the pool of antral follicles from which the ovulatory ones are selected. Precocious development of follicles is also associated with more ovulations, as is the case with the Booroola due to the single gene acting through bone morphogenetic proteins (BMPs). It is well established that ovulation rate can also be influenced by exogenous hormone administration and by environmental factors such as nutrition. It has become apparent that these nuritional effects are mediated by a direct action at the level of the ovary, involving insulin, insulin-like growth factors (IGF) I and II and their binding proteins among other factors. These factors can also affect the quality of the oocyte and consequently embryo development and survival. Recently, the regulation of follicular angiogenesis has been shown to be important for the development of ovulatory follicles, particularly vascular endothelial growth factor (VEGF) which is produced primarily by the granulosa cells within the ovary and can be stimulated by gonadotrophins. Administration of VEGF has been shown to stimulate pre-antral follicular growth and increase the number of pre-ovulatory follicles. In summary both extra- and intra-ovarian factors are involved in the control of ovulation rate. Manipulation of the angiogenic process may also provide new opportunities for regulating the quality and number of follicles that ovulate.

Animal Nutritional Physiological Phenomena↗
PubMed2004

Effect of nutrient intake during pregnancy on fetal and placental growth and vascular development.

Remarkable diversity of size and health of offspring exists after normal pregnancies. When pregnancies are complicated by an extrinsic variable such as inappropriate maternal nutrition, birth weight and health of the neonate are substantially affected. The placenta is the organ through which respiratory gases, nutrients, and wastes are exchanged between the maternal and fetal systems. Thus, transplacental exchange provides for all the metabolic demands of fetal growth. Transplacental exchange is dependent upon uterine and umbilical blood flow, and blood flow rates are in turn dependent in large part upon vascularization of the placenta. Therefore, factors that influence placental vascular development will have a dramatic impact on fetal growth and development, and thereby on neonatal mortality and morbidity. Recent work from our laboratories has focused on the effects of nutrient intake during pregnancy on placental growth and vascular development. Both nutrient restriction of the adult dam and overnourishment of the adolescent dam during pregnancy suppress placental cell proliferation and vascularity. Furthermore, placental expression of angiogenic factors and their receptors, factors that are known to affect vascular growth, are perturbed by level of nutrition. Studies in this area will lead to improved methods to manage nutritionally-compromised pregnancies.

Animal Nutritional Physiological Phenomena↗
PubMed2006

Maternal nutrient restriction upregulates growth signaling pathways in the cotyledonary artery of cow placentomes.

This study evaluated the role of MAPK/ERK1/2 and/or PI3-K/Akt signaling pathways in modulating bovine placentomal vascularity in response to maternal nutrient restriction. Beef cows were randomly assigned to control fed (Control, n=15, 100% of requirements) or nutrient restricted (NR, n=15, 50% requirements) diets from day 30 to day 125 of gestation. Ten cows from each dietary group were necropsied on day 125 (approximately 45% gestation), and the remaining cows in each diet group were then fed control diets and necropsied on day 250 (approximately 90% gestation). At day 125 of gestation, NR cows exhibited increased (P=0.06) COT vascularity, improved (P<0.05) placentome efficiency (fetal weight/placentomal weight), and increased (P<0.05) phosphorylated Akt and ERK1/2 in COT arteries compared to Control cows. By day 250, however, treatment differences in COT vascularity and phosphorylated Akt and ERK1/2 in COT arteries were lost. On both gestational days, no treatment difference was observed in the levels of phosphorylated Akt or ERK1/2 in CAR arteries. CAR vascularity was similar across treatment on day 125, but tended to be greater (P<0.10) in NR than Control cows on day 250. These data suggest that conceptuses react to an early gestational nutrient restriction by up-regulating COT growth signaling pathways associated with angiogenesis, and that these compensations do not persist to term.

Animal Nutritional Physiological Phenomena↗
PubMed1998

Further characterization of a new in vitro angiogenesis model under serum free culture conditions; suppression of endothelial cell differentiation by serum.

We studied the regulation of the extracellular matrix in the recently established murine vascular endothelial cell clones, F-2 or F-2C. F-2 cells constitutively show a cobblestone growth pattern under serum supplemented culture conditions, whereas F-2C cells undergo spontaneous histodifferentiation to form tubular structures in chemically defined media. We reported that the tubulogenesis induced by F-2C might relate to the heavy deposition of a 'basement membrane analog' as a subendothelial matrix (SEM). We further characterized the regulation of extracellular matrix (ECM) metabolism in these cell clones, in terms of gelatinase expression, ECM degradation and the effects of serum. F-2C cells in culture medium containing 1% serum did not undergo tubulogenesis but presented cobblestone growth. Zymography analysis showed that both F-2 and F-2C cells express two gelatinase (72 and 92 kDa). However, F-2 cells mainly expressed the former and faintly the latter, whereas F-2C mainly expressed the latter. Proteolysis studies showed that the spent media conditioned by F-2C cells partially cleaved type IV collagen and completely degraded type V collagen. The cleavage of type V collagen was suppressed by the addition of serum, whereas that of type IV collagen was not. The proteolysis of laminin and fibronectin by the conditioned medium was not observed. Serum-supplemented F-2 or F-2C cultures markedly suppressed SEM deposition. These results indicated that F-2C cells under serum free culture conditions not only present a simple and useful in vitro model with which to study the dynamic processes of proteolysis and ECM metabolism during the sequential phases of angiogenesis, but is also useful for analyzing the serum effects on angiogenesis (AG).

Animals↗
PubMed2001

Muscle adaptation to altitude: tissue capillarity and capacity for aerobic metabolism.

Prolonged exposure to high altitude leads to reduced muscle mass and performance. The fall in muscle mass follows a reduction in fiber size, which at first was believed to be accompanied by increased fiber capillarization and aerobic enzymes. Subsequent studies showed that hypoxia alone does not alter capillary number and geometry in skeletal muscles of mammals at altitude. It was also found that alterations in fiber size and aerobic enzymes depend on a number of additional factors, including animal activity and the level of hypoxia (e.g., moderate vs. extreme altitude). With training at altitude, fiber capillary number and aerobic enzymes are increased, indicating that muscle potential for plasticity is conserved in hypoxia. Recent studies have also shown that capillary number and geometry are altered in muscles of several species of birds native or exposed to higher altitude; that is, that capillary growth can occur in skeletal muscle in response to chronic exposure to high altitude. In this mini review, we summarize these data and current knowledge on muscle capillary to fiber structural relationships and their implications for muscle aerobic function at altitude.

Adaptation, Physiological↗
PubMedDate not supplied

Establishment of vessel-like structures in long-term three-dimensional tissue culture of myocardium: an electron microscopy study.

To assess whether long-term three-dimensional (3D) tissue culture of myocardium enables the in vitro establishment of vessel-like structures, myocardial tissue from newborn mice was incubated under conditions of 3D culture for at least 3 weeks, and studied by phase-contrast microscopy, conventional histology, immunohistochemistry, and electron microscopy. During 3 weeks of culture, a mean 24.35 +/- 3.74% of all aggregates contracted spontaneously. The contracting aggregates displayed a tissue-like architecture with small basal and apical zones, and a large central zone. The basal and apical zone consisted of immature mesenchymal cells. The underlying shell of the aggregate contained many cardiomyocytes. Vessel-like structures were found concentrated within the aggregates. Immunohistochemistry showed that up to 15% of the cells in the central zone of the aggregate were positive for the endothelial-specific BS-I lectin. Vessel-like structures were formed by cells, which often showed intracytoplasmatic lumena. Surrounding the neocapillaries, structures of a rudimentary basal membrane could be detected. A 3D culture of myocardial tissue permits the establishment of a rudimentary capillary network within the tissue aggregates, which presumably guarantees a sufficient tissue perfusion up to a maximum aggregate diameter of approximately 900 microm.

Adaptation, Physiological↗
PubMedDate not supplied

Adaptation of tissue to a chronic heat load.

Determination of the chronic effect of heat on tissue is one of the important issues facing mechanically actuated total artificial heart (TAH) development. In an effort to characterize this effect, implantations of heating devices producing constant heat fluxes of 0.04 watts/cm2, 0.06 W/cm2, and 0.08 W/cm2 were performed in 11 calves (H-series). Heated disks were implanted adjacent to lung and muscle tissue for a period of 7 weeks. Temperature sensors were placed at the surface as part of the heater assemblies. The results showed that initially, temperature elevations above body temperature (delta T) were 6.4 +/- 0.6 degrees C, 4.5 +/- 0.2 degrees C, and 1.8 +/- 0.5 degrees C at the muscle heater surface for 0.08, 0.06, and 0.04 W/cm2, respectively. At 2 weeks after implant delta T values changed to 5.5 +/- 0.6 degrees C, 3.4 +/- 0.2 degrees C, and 1.8 +/- 0.2 degrees C, respectively. Seven weeks after implant, delta T values decreased to 3.7 +/- 1.2 degrees C, 2.8 +/- 0.1 degrees C, and 0.8 degrees C for 0.08, 0.06, and 0.04 W/cm2, respectively. The authors think this change is attributable to an adaptive response of the tissue to increase heat dissipation through angiogenesis. Results from three TAH cases indicated that at two measured tissue interfaces, delta T decreased by 1 degrees C during a 15 day period. At the same time, the waste heat (volts x current in-flow x afterload to the blood) remained constant at 11.1 +/- 0.5 W during this period. This decrease in delta T corresponded to that observed for the H-series experiments at the higher heat fluxes. Thus, it appears that adaptation observed in the H-series experiments also is seen for tissues surrounding heat sources such as the TAH.

Adaptation, Physiological↗
PubMed1997

[Arterialization of the capillary network in the left ventricular subendocardium in young rats subjected to exercise training].

The increase in cardiac activity requires an increase in oxygen supply to the ventricular tissues. Two adaptational changes in the capillary network seem to increase the oxygen supply; one is the increase in capillary density and the other may be the increase in arteriolar capillaries. To test this hypothesis, double staining method, which was validated by microsphere injection, was used for differentiation of arteriolar and venular capillaries in exercise-trained rats in the present study. Male Wistar rats after weaning (3 weeks old) were subjected to treadmill running 1 hour/day in the evening, 6 days/week. The running speed was increased from 10 m/min without gradient to 25 m/min with a 7% gradient for 6 weeks. The total capillary density and capillary to myocyte ratio increased significantly. Capillary domain area decreased, suggesting neoformation of capillaries. In support of the capillary increase two stimulators for angiogenesis, vascular endothelial growth factor and basic fibroblast growth factor were immunohistochemically stained in the ventricular tissues from exercise-trained rats. Capillary of arteriolar type increased with a decrease in the venular capillary. The arteriolar portion of capillaries became significantly longer and the venular portion shorter than in resting control rats. Branching of capillaries increased both in the arteriolar and venular portions. These results suggest that the arterialization of capillary network proceeded with the increase in the capillary density to facilitate the oxygen transport to cardiac tissues.

Adaptation, Physiological↗
PubMed2006

Wnt/Frizzled signaling in the vasculature: new angiogenic factors in sight.

Wnt growth factors function via Frizzled receptors to affect cellular proliferation, differentiation, apoptosis, and migration. Wnt/Frizzled signaling is now linked to human hereditary disorders with retinal vascular defects, implicating Wnts as angiogenic factors. Here, we discuss Wnts and a novel Frizzled ligand, Norrin, in physiological and pathological angiogenesis.

Angiogenesis Inducing Agents↗
PubMed1995

Quantitative analysis of angiogenesis and growth of bone: effect of indomethacin exposure in a combined in vitro-in vivo approach.

Nonsteroidal anti-inflammatory agents have been used experimentally and clinically to suppress a variety of physiological events, including angiogenesis and formation of bone. The exact mechanisms by which indomethacin alters skeletal tissue generation are unknown, due in part to methodological limitations. By the use of an organ culture assay and an animal model using intravital microscopy in mice bearing dorsal skinfold chambers, the effect of indomethacin on growth and angiogenesis of neonatal femora was characterized over 16 days. In both assays, femora significantly elongated with time (P < 0.05). The in vitro growth rate was more rapid than in vivo and dependent on the serum concentration, culture medium and age of mice. Although enhancing the serum content promoted cellular proliferation in organ culture, it dose-dependently suppressed femoral elongation, leading at 20% fetal calf serum to growth rates identical to those observed in vivo. Indomethacin supplementation (2 and 10 mg l-1) significantly accelerated longitudinal femoral growth in organ culture (P < 0.05), whereas in vivo indomethacin (2 mg kg-1) did not modulate either angiogenesis or elongation of bone. Our in vitro data propose a central role of serum in the regulation of bone formation. Although indomethacin altered femoral growth in vitro, our findings do not suggest that indomethacin suppresses angiogenesis or growth of bone in vivo. The complexity of physiological events in vivo may be obscuring a detectable effect.

Animals↗
PubMed2003

A novel role for erythropoietin during fibrin-induced wound-healing response.

In this study, we investigated the role of the hematopoietic cytokine erythropoietin (EPO) during wound healing, the physiological response to tissue injury. We used an in vivo wound-healing assay (fibrin Z-chambers) consisting of fibrin-filled chambers implanted subcutaneously in rats. The fibrin inside the chambers is replaced by granulation tissue consisting of new blood vessels, macrophages and fibroblasts as part of the wound-healing response. Local, exogenous recombinant EPO administration into the fibrin matrix significantly increased granulation tissue formation in a dose-dependent manner. To investigate the physiological role of endogenous EPO during wound healing, we used soluble EPO receptor or anti-EPO monoclonal antibodies to neutralize EPO and observed dose-dependent inhibition of granulation tissue formation, consistent with an important role for EPO in the wound-healing cascade. The ability of recombinant EPO to promote wound healing was associated with a proangiogenic effect during granulation tissue formation. We also found abundant expression of EPO receptor protein in macrophages, cells that play a pivotal role during wound healing. Modulation of wound healing because of administration of recombinant EPO or inhibition of endogenous EPO-EPO receptor correlated with changes in levels of inducible nitric oxide synthase protein in granulation tissue. These data demonstrate a novel function for EPO by providing in vivo evidence for a physiological role during fibrin-induced wound healing.

Animals↗
PubMed2002

Structure and function of collagen-derived endostatin inhibitors of angiogenesis.

Endostatins are inhibitors of endothelial cell migration and angiogenesis and have been shown to reduce tumor growth in animal models. They are derived from the nontriplehelical C-terminal NC1 domains of collagens XV and XVIII, which are released proteolytically in trimeric form and further converted to monomeric endostatins of about 20 kDa. Both endostatin isoforms share a compact globular fold, but differ in certain binding properties for proteins and cells, as well as in tissue distribution. Differences in activity were found between NC1 domains and endostatins and are related to the oligomerization state. Endostatin effects are not restricted to endothelial cells, but also control renal epithelial cells and neuronal guidance in C. elegans. Cellular receptors are still insufficiently characterized and include for endostatin-XVIII heparan sulfate proteoglycans. Receptor engagement elicits various downstream effects including tyrosine kinase and gene activation. Much remains to be learned, however, about details of the signal transduction cascades and how they interfere with pro-angiogenic factors under physiological conditions and during therapeutic treatment.

Animals↗
PubMed1999

Modeling of the parenchymous vascularization and perfusion.

RATIONALE AND OBJECTIVES: The authors sought to create a realistic model of the parenchymous vascularization and perfusion. METHODS: A three-dimensional vascular model has been developed that reproduces the growth process of a vascular tree (angiogenesis). This model follows physical laws related to blood flow in vessels (Poiseuille's law), takes into account anatomic constraints, and optimizes a cost function related to the blood volume. RESULTS: Vascular trees, the ramifications of which go from main arteries to small arterioles, were simulated. Vascular structures corresponding to either a normal tissue perfusion or an abnormal perfusion (for example, a local hypervascularization) were presented in three dimensions (volume rendering). Geometric and hemodynamic characteristics computed on these trees were consistent with those of real data found in the literature. The vascular model is also a good tool for studying the propagation of the contrast product in normal and abnormal vessels. CONCLUSIONS: The three-dimensional vascular model presented in this article provides insight into the simulation and the understanding of anatomic or physiologic vascular modifications.

Blood Vessels↗
PubMed2002

Enhanced myocyte-based biosensing of the blood-borne signals regulating chronotropy.

Biosensors play a critical role in the real-time determination of relevant functional physiological needs. However, typical in vivo biosensors only approximate endogenous function via the measurement of surrogate signals and, therefore, may often lack a high degree of dynamic fidelity with physiological requirements. To overcome this limitation, we have developed an excitable tissue-based implantable biosensor approach, which exploits the inherent electropotential input-output relationship of cardiac myocytes to measure the physiological regulatory inputs of chronotropic demand via the detection of blood-borne signals. In this study, we report the improvement of this application through the modulation of host-biosensor communication via the enhancement of vascularization of chronotropic complexes in mice. Moreover, in an effort to further improve translational applicability as well as molecular plasticity, we have advanced this approach by employing stem cell-derived cardiac myocyte aggregates in place of whole cardiac tissue. Overall, these studies demonstrate the potential of biologically based biosensors to predict endogenous physiological dynamics and may facilitate the translation of this approach for in vivo monitoring.

Animals↗
PubMed2002

Myocardial capillary angiogenesis and coronary flow in ischemia tolerance rat by adaptation to intermittent high altitude hypoxia.

AIM: To determine the effects of simulated intermittent high altitude hypoxia adaptation (IHA) on coronary capillary and coronary flow (CF) in rat hearts. METHODS: Model of Langendorf-perfused isolated rat hearts were used to measure CF during ischemia-reperfusion, and immunoperoxidase staining assay and computer-aid morphometry analysis were conducted to determine the myocardial capillary densities. Cyclic GMP (cGMP) level in myocardium was measured by radio-immunoassay. RESULTS: Pre-ischemia level of CF in IHA rats was higher (IHA28 13.4 mL/min+/-1.5 mL/min, IHA42 15.4 mL/min+/-2.0 mL/min, P < 0.01) than that of normoxic rats (11.0+/-0.8) mL/min, and the recovery of CF after ischemia-reperfusion was better in IHA rats. As an adaptive result, the myocardial capillary densities of the left ventricular myocardium in IHA rats were 1.5 times of those in normoxic control rats, but there was no apparent ventricular hypertrophy in IHA rats. Myocardial cGMP content (1.8+/-0.7) nmol/g in IHA rats were increased significantly compared with control rats (1.1+/-0.4) nmol/g, but cGMP level was not altered before and after ischemia-reperfusion in either group. It was also revealed that in isolated rat hearts perfused, myocardial function recovered better in IHA rats than that in normoxic control rats. CONCLUSION: IHA adaptation increased the tolerance of rat hearts against subsequent ischemia-reperfusion injury, and increase in coronary circulation and angiogenesis might be the mechanisms of myocardium protected by IHA.

Adaptation, Physiological↗