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1.
Background
It has been previously suggested that angiogenesis occurs during the menstrual cycle. Moreover, a rise in uterine blood flow is largely maintained by vasodilatation and substantial increases in angiogenesis. It is known that estradiol (E2) and progesterone (P4) are involved in angiogenesis. Recently, endothelial progenitor cells (EPCs) were found to be involved in neovascularization; however, their roles in uterine neovascularization have not been well characterized. We hypothesized that E2- or P4-mediated EPC proliferation plays important roles in uterine neovascularization during the menstrual cycle. 相似文献2.
Studying the growth of cervical carcinoma nests and angiogenesis by immunostaining, quantitation and three-dimensional structural analysis 总被引:2,自引:0,他引:2
Chen YY Li YL Li CJ Li YL Chen LP Jiang YP Gao H Takahashi T Yaegash H 《Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology》2000,22(1):80-84
OBJECTIVE: To analyze the relationship and mutual effect of the growth of cervical carcinoma nests and angiogenesis. STUDY DESIGN: Serial paraffin sections of cervical squamous carcinoma were stained in repeated order with hematoxylin-eosin (HE), immunostain for factor VIII-related antigen, type IV collagen and proliferating cell nuclear antigen (PCNA). Three-dimensional reconstructions were made, and the volumes of carcinoma nests, necrosis and microvessels were measured. RESULTS: Two types of cervical carcinoma nests were distinguished on the basis of their growth characteristics and vascularity (groups I and II). Group I nests: The carcinoma cells were proliferating actively, as determined by their morphology and PCNA staining. There were abundant microvessels. Some endothelial sprouts and cords penetrated the nests and then formed networks and new vessels. The volume ratio of microvessels, including sprouts and cords, to the nests was 0.6282:1. Group II nests: The center of these nests underwent necrosis. The peripheral cells were rather small, with no mitosis. The PCNA index was rather low; these nests grew very slowly. There were only a few surrounding microvessels with no endothelial sprouts or cords. The volume ratio of vessels to nest was 0.0657:1. CONCLUSION: Two types of cervical carcinoma nests show a close relationship and mutual effect of the growth of carcinoma nest and angiogenesis. Group I nests grow and develop well, with abundant microvessels. Thus, many tumor cells may be angiogenic and induce angiogenesis; growth of the nests seemed dependent on adequate neovascularization. Group II nests grow slowly, with a few microvessels; the center of the nests undergoes necrosis. The inadequate blood supply must be one of the important causes of necrosis. Considering that there must have been abundant neovascularization during their growth in the past, most of the microvessels must have been obliterated and then reabsorbed to make the remaining vessels so few. 相似文献
3.
Chetan Lakshmana Reddy Nejla Yosef Eroboghene E. Ubogu 《Cellular and molecular neurobiology》2013,33(6):789-801
Several mitogens such as vascular endothelial growth factor (VEGF) have been implicated in mammalian vascular proliferation and repair. However, the molecular mediators of human blood-nerve barrier (BNB) development and specialization are unknown. Primary human endoneurial endothelial cells (pHEndECs) were expanded in vitro and specific mitogen receptors detected by western blot. pHEndECs were cultured with basal medium containing different mitogen concentrations with or without heparin. Non-radioactive cell proliferation, Matrigel?-induced angiogenesis and sterile micropipette injury wound healing assays were performed. Proliferation rates, number and total length of induced microvessels, and rate of endothelial cell monolayer wound healing were determined and compared to basal conditions. VEGF-A165 in the presence of heparin, was the most potent inducer of pHEndEC proliferation, angiogenesis, and wound healing in vitro. 1.31 nM VEGF-A165 induced ~110 % increase in cell proliferation relative to basal conditions (~51 % without heparin). 2.62 pM VEGF-A165 induced a three-fold increase in mean number of microvessels and 3.9-fold increase in total capillary length/field relative to basal conditions. In addition, 0.26 nM VEGF-A165 induced ~1.3-fold increased average rate of endothelial wound healing 4–18 h after endothelial monolayer injury, mediated by increased cell migration. VEGF-A165 was the only mitogen capable of complete wound closure, occurring within 30 h following injury via increased cell proliferation. This study demonstrates that VEGF-A165, in the presence of heparin, is a potent inducer of pHEndEC proliferation, angiogenesis, and wound healing in vitro. VEGF-A165 may be an important mitogen necessary for human BNB development and recovery in response to peripheral nerve injury. 相似文献
4.
Juan-Carlos Pelayo Nicholas A. Veldhuis Emily M. Eriksson Nigel W. Bunnett Daniel P. Poole 《Cell and tissue research》2014,356(2):319-332
The substance P neurokinin 1 receptor (NK1R) regulates motility, secretion, inflammation and pain in the intestine. The distribution of the NK1R is a key determinant of the functional effects of substance P in the gut. Information regarding the distribution of NK1R in subtypes of mouse enteric neurons is lacking and is the focus of the present study. NK1R immunoreactivity (NK1R-IR) is examined in whole-mount preparations of the mouse distal colon by indirect immunofluorescence and confocal microscopy. The distribution of NK1R-IR within key functional neuronal subclasses was determined by using established neurochemical markers. NK1R-IR was expressed by a subpopulation of myenteric and submucosal neurons; it was mainly detected in large multipolar myenteric neurons and was colocalized with calcitonin gene-related peptide, neurofilament M, choline acetyltransferase and calretinin. The remaining NK1R-immunoreactive neurons were positive for nitric oxide synthase. NK1R was expressed by most of the submucosal neurons and was exclusively co-expressed with vasoactive intestinal peptide, with no overlap with choline acetyltransferase. Treatment with substance P resulted in the concentration-dependent internalisation of NK1R from the cell surface into endosome-like structures. Myenteric NK1R was mainly expressed by intrinsic primary afferent neurons, with minor expression by descending interneurons and inhibitory motor neurons. Submucosal NK1R was restricted to non-cholinergic secretomotor neurons. These findings highlight key differences in the neuronal distribution of NK1R-IR between the mouse, rat and guinea-pig, with important implications for the functional role of NK1R in regulating intestinal motility and secretion. 相似文献
5.
Huan Wang Ling-Juan Hong Ji-Yun Huang Quan Jiang Rong-Rong Tao Chao Tan Nan-Nan Lu Cheng-Kun Wang Muhammad M Ahmed Ying-Mei Lu Zhi-Rong Liu Wei-Xing Shi En-Yin Lai Christopher S Wilcox Feng Han 《Cell research》2015,25(6):674-690
Septic encephalopathy (SE) is a critical factor determining sepsis mortality. Vascular inflammation is known to be involved in SE, but the molecular events that lead to the development of encephalopathy remain unclear. Using time-lapse in vivo two-photon laser scanning microscopy, we provide the first direct evidence that cecal ligation and puncture in septic mice induces microglial trafficking to sites adjacent to leukocyte adhesion on inflamed cerebral microvessels. Our data further demonstrate that septic injury increased the chemokine CXCL1 level in brain endothelial cells by activating endothelial P2RX7 and eventually enhanced the binding of Mac-1 (CD11b/CD18)-expressing leukocytes to endothelial ICAM-1. In turn, leukocyte adhesion upregulated endothelial CX3CL1, thereby triggering microglia trafficking to the injured site. The sepsis-induced increase in endothelial CX3CL1 was abolished in CD18 hypomorphic mutant mice. Inhibition of the P2RX7 pathway not only decreased endothelial ICAM-1 expression and leukocyte adhesion but also prevented microglia overactivation, reduced brain injury, and consequently doubled the early survival of septic mice. These results demonstrate the role of the P2RX7 pathway in linking neurovascular inflammation to brain damage in vivo and provide a rationale for targeting endothelial P2RX7 for neurovascular protection during SE. 相似文献
6.
Millet Régis Goossens Jean-François Bertrand-Caumont Karine Chavatte Philippe Houssin Raymond Hénichart Jean-Pierre 《International journal of peptide research and therapeutics》1999,6(4):221-233
Summary Chemical modifications on the NK1 competitive antagonist L-732,138, with a view to creating a dual NK1/NK2 ligand, led to the tryptophan derivative 1 possessing the protected Gly-Leu sequence of the C-terminus of substance P and
neurokinin A. Modifications in the nature of the carbamate function increased the selectivity for the NK1 receptor, whereas the inclusion of the indole moiety in β-carboline or carbazole rings decreased the affinity for both receptors.
Free indolylmethyl and Cbz carbamate groups were shown to be essential for NK2 affinity. 相似文献
7.
Katelijne O De Swert Ken R Bracke Tine Demoor Guy G Brusselle Guy F Joos 《Respiratory research》2009,10(1):37
Background
The tachykinins, substance P and neurokinin A, present in sensory nerves and inflammatory cells such as macrophages and dendritic cells, are considered as pro-inflammatory agents. Inflammation of the airways and lung parenchyma plays a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and increased tachykinin levels are recovered from the airways of COPD patients. The aim of our study was to clarify the involvement of the tachykinin NK1 receptor, the preferential receptor for substance P, in cigarette smoke (CS)-induced pulmonary inflammation and emphysema in a mouse model of COPD.Methods
Tachykinin NK1 receptor knockout (NK1-R-/-) mice and their wild type controls (all in a mixed 129/sv-C57BL/6 background) were subjected to sub acute (4 weeks) or chronic (24 weeks) exposure to air or CS. 24 hours after the last exposure, pulmonary inflammation and development of emphysema were evaluated.Results
Sub acute and chronic exposure to CS resulted in a substantial accumulation of inflammatory cells in the airways of both WT and NK1-R-/- mice. However, the CS-induced increase in macrophages and dendritic cells was significantly impaired in NK1-R-/- mice, compared to WT controls, and correlated with an attenuated release of MIP-3α/CCL20 and TGF-β1. Chronic exposure to CS resulted in development of pulmonary emphysema in WT mice. NK1-R-/- mice showed already enlarged airspaces upon air-exposure. Upon CS-exposure, the NK1-R-/- mice did not develop additional destruction of the lung parenchyma. Moreover, an impaired production of MMP-12 by alveolar macrophages upon CS-exposure was observed in these KO mice. In a pharmacological validation experiment using the NK1 receptor antagonist RP 67580, we confirmed the protective effect of absence of the NK1 receptor on CS-induced pulmonary inflammation.Conclusion
These data suggest that the tachykinin NK1 receptor is involved in the accumulation of macrophages and dendritic cells in the airways upon CS-exposure and in the development of smoking-induced emphysema. As both inflammation of the airways and parenchymal destruction are important characteristics of COPD, these findings may have implications in the future treatment of this devastating disease. 相似文献8.
A. I. Krupatkin 《Human physiology》2007,33(5):595-602
We used laser Doppler flowmetry with wavelet analysis of blood flow oscillations, computer capillaroscopy, and thermometry of the nail bed in 30 subjects to show an important role of the oscillatory circuit in the regulation of capillary hemodynamics, number of functioning capillaries, and linear and volumetric velocity of blood flow. The number of functioning capillaries is regulated by oscillations of myogenic and sensory peptidergic origin. The appearance of sensory oscillations, especially high-amplitude oscillations, is an adaptive neurotrophic mechanism that significantly increases the number of functioning capillaries and intensity of blood flow from arterioles to capillaries. The linear velocity of blood flow depends on both the tone of microvessels and changes in the dynamic component of blood pressure. Under conditions of skin hypoperfusion, the mean linear velocity of capillary blood flow may be inversely related to the extracapillary perfusion, including the amplitude of heart rate (A h) and oscillations of the tone of precapillary sphincters, whereas under conditions of vasodilation and increased skin perfusion, it may be inversely related to the amplitude of arteriolar oscillations of endothelial or neurogenic sympathetic origin (A maxe + n) and the shunting index. The A h affects the linear velocity of blood flow in the arterial part of capillaries, whereas the A maxe + n influences the same factor in the venous part. The contribution of oscillations to the regulation of the linear velocity varies depending on the perfusion and skin temperature. The resultant tone of distributing microvessels is determined by the competition between the stationary and oscillatory components. In addition to changes in the amplitude, the frequency of vasomotions may also be important. The regulatory importance of the oscillatory circuit is increased with a decrease in the skin blood flow. 相似文献
9.
Régis Millet Jean-François Goossens Karine Bertrand-Caumont Philippe Chavatte Raymond Houssin Jean-Pierre Hénichart 《Letters in Peptide Science》1999,6(4):221-233
Chemical modifications on the NK1 competitive antagonist L-732,138, with a view to creating a dual NK1/NK2 ligand, led to the tryptophan derivative 1 possessing the protected Gly-Leu sequence of the C-terminus of substance P and neurokinin A. Modifications in the nature of the carbamate function increased the selectivity for the NK1 receptor, whereas the inclusion of the indole moiety in -carboline or carbazole rings decreased the affinity for both receptors. Free indolylmethyl and Cbz carbamate groups were shown to be essential for NK2 affinity. 相似文献
10.
11.
K. M. Jenkinson Jan M. Morgan John B. Furness Bridget R. Southwell 《Histochemistry and cell biology》1999,112(3):233-246
The localisation of NK3 tachykinin receptors in guinea-pig ileum was studied using the fluorescently labelled agonists, Cy3.5-neurokinin A and Cy3.5-kassinin.
Binding to nerve cell bodies in the myenteric and submucosal plexuses was visualised using confocal microscopy. Binding to
NK1 receptors was blocked by the NK1 receptor antagonist, CP-99994. NK3 receptors, demonstrated by binding in the presence of CP-99994, occurred in 72% of myenteric and 38% of submucosal neurons.
Colocalisation with other markers was examined to deduce the classes of neurons with NK3 receptors. In myenteric ganglia, NK3 receptors were present on the following: 73% of calbindin-immunoreactive (IR) intrinsic primary afferent neurons, 63% of
calretinin-IR excitatory motor neurons and ascending interneurons, 63% of nitric oxide synthase-IR inhibitory motor neurons
and descending interneurons, 79% of strongly neuropeptide Y (NPY)-IR secretomotor neurons, 67% of weakly NPY-IR descending
interneurons and motor neurons, and 46% of NK1 receptor-IR neurons. In submucosal ganglia, NK3 receptors were on 65% of calretinin-IR secretomotor/vasodilator neurons, 81% of NPY-IR cholinergic secretomotor neurons,
2% of vasoactive intestinal peptide-IR non-cholinergic secretomotor neurons and were completely absent from substance P-IR
intrinsic primary afferent neurons. The results support physiological studies suggesting that NK3 receptors mediate tachykinin transmission between myenteric sensory neurons and to interneurons and/or motor neurons in descending
inhibitory and ascending excitatory pathways.
Accepted: 22 June 1999 相似文献
12.
13.
Esipov R Beyrakhova K Likhvantseva V Stepanova E Stepanenko V Kostromina M Abramchik Y Miroshnikov A 《Biochimie》2012,94(6):1368-1375
Tumstatin, a cleavage fragment of collagen IV, is a potent endogenous inhibitor of angiogenesis. Tumstatin-derived peptide T8 possesses all angiostatic properties of full-length tumstatin and indirectly suppresses tumor growth. The potential of T8 to block pathological angiogenesis in the eye has not been explored yet. Here we assess antiangiogenic effects of a recombinant T8 peptide in rabbit corneal neovascularization models. The fusion protein consisting of T8 and thioredoxin was synthesized in a highly efficient Escherichia coli expression system, isolated using ion-exchange chromatography and cleaved with TEV (tobacco etch virus) protease. The target peptide was purified on an anion-exchange resin and by reversed phase high-performance liquid chromatography. The recombinant peptide suppressed the proliferation of basic fibroblast growth factor-induced SVEC-4-10 endothelial cells (simian virus 40-immortalized murine endothelial cells) and inhibited tube formation in these cells in a dose-dependent manner. In rabbit corneal neovascularization models T8 demonstrated the ability to prevent pathological angiogenesis (when injected simultaneously with the induction of neovascularization) and, moreover, to promote the regression of newly-formed blood vessels (when injected on day 8 after angiogenesis stimulation). Our results suggest that T8 may have a therapeutic potential in the treatment of ocular neovascular diseases. 相似文献
14.
The formation of new capillaries from existing blood vessels is critical for tumor growth and metastasis. In this study we
report that amentoflavone, a biflavonoid from Biophytum sensitivum, could inhibit the process of angiogenesis. Amentoflavone at nontoxic concentrations (0.05–0.2 μg/ml) showed significant
inhibition in the proliferation, migration, and tube formation of endothelial cells, which are key events in the process of
angiogenesis. In vivo studies in C57BL/6 mice using amentoflavone showed remarkable inhibition (52.9%) of tumor directed capillary formation. Amentoflavone
showed inhibitory effect on the production of various endogenous factors such as IL-1β, IL-6, TNF-α, GM-CSF, and VEGF that
control the process of angiogenesis. Amentoflavone treatment could increase the production of IL-2 and TIMP-1, which could
successfully shift the equilibrium towards an angiostatic condition. The antiangiogenic activity of amentoflavone was supported
by its remarkable suppression in sprouting of microvessels from rat aorta. Our results also show that amentoflavone could
inhibit the production of VEGF mRNA in B16–F10 cells. These findings indicate that amentoflavone inhibits angiogenesis by
disrupting the integrity of endothelial cells and by altering the endogenous factors that are required for the process of
neovascularization.
Published in Russian in Biokhimiya, 2008, Vol. 73, No. 2, pp. 258–269. 相似文献
15.
Netrins are secreted molecules involved in axon guidance and angiogenesis. However, the role of netrins in the vasculature remains unclear. Netrin-4 and netrin-1 have been found to be either pro- or antiangiogenic factors. Previously, we found that netrin-1 acts as an anti-angiogenic factor in rats by inhibiting alkali burn-induced corneal neovascularization. Here, we further investigate the effects of netrin-4, another member of the same netrin family, on neovascularization in vitro and in vivo. We found that netrin-4 functions similarly as netrin-1 in angiogenesis. In vitro angiogenesis assay shows that netrin-4 affected human umbilical vein endothelial cell (HUVEC) tube formation, viability and proliferation, apoptosis, migration, and invasion in a dose-dependent manner. Netrin-4 was topically applied in vivo to alkali-burned rat corneas on day 0 (immediately after injury) and/or day 10 post-injury. Netrin-4 subsequently suppressed and reversed corneal neovascularization. Netrin-4 inhibited corneal epithelial and stromal cell apoptosis, inhibited vascular endothelial growth factor (VEGF), but promoted pigment epithelium-derived factor (PEDF) expression, decreased NK-KB p65 expression, and inhibits neutrophil and macrophage infiltration. These results indicate that netrin-4 shed new light on its potential roles in treatmenting for angiogenic diseases that affect the ocular surface, as well as other tissues. 相似文献
16.
Blood vessels either form de novo through the process of vasculogenesis or through angiogenesis that involves the sprouting and proliferation of endothelial cells in pre-existing blood vessels. A complex interactive network of signaling cascades downstream from at least three of the nine known G-protein-coupled sphingosine-1-phosphate (S1P) receptors act as a prime effector of neovascularization that occurs in embryonic development and in association with various pathologies. This review focuses on the current knowledge of the roles of S1P signaling in vasculogenesis and angiogenesis, with particular emphasis on vascular cell adhesion and motility responses. 相似文献
17.
Shin D Garcia-Cardena G Hayashi S Gerety S Asahara T Stavrakis G Isner J Folkman J Gimbrone MA Anderson DJ 《Developmental biology》2001,230(2):139-150
The transmembrane ligand ephrinB2 and its receptor tyrosine kinase EphB4 are molecular markers of embryonic arterial and venous endothelial cells, respectively, and are essential for angiogenesis. Here we show that expression of ephrinB2 persists in adult arteries where it extends into some of the smallest diameter microvessels, challenging the classical view that capillaries have neither arterial nor venous identity. EphrinB2 also identifies arterial microvessels in several settings of adult neovascularization, including tumor angiogenesis, contravening the dogma that tumor vessels arise exclusively from postcapillary venules. Unexpectedly, expression of ephrinB2 also defines a stable genetic difference between arterial and venous vascular smooth muscle cells. These observations argue for revisions of classical concepts of capillary identity and the topography of neovascularization. They also imply that ephrinB2 may be functionally important in neovascularization and in arterial smooth muscle, as well as in embryonic angiogenesis. 相似文献
18.
Fibroblast Growth Factor-2 (FGF-2) Induces Vascular Endothelial Growth Factor (VEGF) Expression in the Endothelial Cells of Forming Capillaries: An Autocrine Mechanism Contributing to Angiogenesis 总被引:18,自引:0,他引:18
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Graziano Seghezzi Sundeep Patel Christine J. Ren Anna Gualandris Giuseppe Pintucci Edith S. Robbins Richard L. Shapiro Aubrey C. Galloway Daniel B. Rifkin Paolo Mignatti 《The Journal of cell biology》1998,141(7):1659-1673
FGF-2 and VEGF are potent angiogenesis inducers in vivo and in vitro. Here we show that FGF-2 induces VEGF expression in vascular endothelial cells through autocrine and paracrine mechanisms. Addition of recombinant FGF-2 to cultured endothelial cells or upregulation of endogenous FGF-2 results in increased VEGF expression. Neutralizing monoclonal antibody to VEGF inhibits FGF-2–induced endothelial cell proliferation. Endogenous 18-kD FGF-2 production upregulates VEGF expression through extracellular interaction with cell membrane receptors; high-Mr FGF-2 (22–24-kD) acts via intracellular mechanism(s). During angiogenesis induced by FGF-2 in the mouse cornea, the endothelial cells of forming capillaries express VEGF mRNA and protein. Systemic administration of neutralizing VEGF antibody dramatically reduces FGF-2-induced angiogenesis. Because occasional fibroblasts or other cell types present in the corneal stroma show no significant expression of VEGF mRNA, these findings demonstrate that endothelial cell-derived VEGF is an important autocrine mediator of FGF-2-induced angiogenesis. Thus, angiogenesis in vivo can be modulated by a novel mechanism that involves the autocrine action of vascular endothelial cell-derived FGF-2 and VEGF. 相似文献
19.
Summary Electrical stimulation of efferent thoracic vagus nerve (TVN) evoked neurogenic inflammation in respiratory tract of atropine-treated
rats by an undefined mechanism. We explored whether efferent TVN stimulation via substance P facilitates neurogenic inflammation
via action of nuclear factor-κB (NF-κB) activation and reactive oxygen species (ROS) production. Our results showed that increased
frequency of TVN stimulation concomitantly increased substance P-enhanced hypotension, and bronchoconstriction (increases
in smooth muscle electromyographic activity and total pulmonary resistance). The enhanced SP release evoked the appearance
of endothelial gap in silver-stained leaky venules, India-ink labeled extravasation, and accumulations of inflammatory cells
in the respiratory tract, contributing to trachea plasma extravasation as well as increases in blood O2− and H2O2 ROS amount. L-732138 (NK1 receptor antagonist), SR-48968 (NK2 receptor antagonist), dimethylthiourea (H2O2 scavenger) or catechins (O2− and H2O2 scavenger) pretreatment reduced efferent TVN stimulation-enhanced hypotension, bronchoconstriction, and plasma extravasation.
Increased frequency of TVN stimulation significantly upregulated the expression of nuclear factor-κB (NF-κB) in nuclear protein
and intercellular adhesion molecule-1 (ICAM-1) in total protein of the lower respiratory tract tissue. The upregulation of
NF-κB and ICAM-1 was attenuated by NK receptor antagonist and antioxidants. In conclusion, TVN efferent stimulation increases
substance P release to trigger NF-κB mediated ICAM-1 expression and O2− and H2O2 ROS production in the respiratory tract. 相似文献
20.
Endothelial cells in vivo are constantly exposed to shear associated with blood flow and altered shear stress elicits cellular
responses (mechanotransduction). This review describes the role of shear sensors and signal transducers in these events. The
major focus is the response to removal of shear as occurs when blood flow is compromised (i.e., ischemia). Pulmonary ischemia
studied with the isolated murine lung or flow adapted pulmonary microvascular endothelial cells in vitro results in endothelial
generation of reactive oxygen species (ROS) and NO. The response requires caveolae and is initiated by endothelial cell depolarization
via KATP channel closure followed by activation of NADPH oxidase (NOX2) and NO synthase (eNOS), signaling through MAP kinases, and
endothelial cell proliferation. These physiological mediators can promote vasodilation and angiogenesis as compensation for
decreased tissue perfusion. 相似文献