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Results for “Neovascularization, Physiologic”

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PubMed2002

Angiogenesis and mineralization during distraction osteogenesis.

Distraction osteogenesis is currently a standard method of bone lengthening. It is a viable method for the treatment of short extremities as well as extensive bone defects, because large amounts of bone can be regenerated in the distraction gap. Mechanical stimulation by distraction induces biological responses of skeletal regeneration that is accomplished by a cascade of biologic processes that may include differentiation of pluripotential tissue, angiogenesis, mineralization, and remodeling. There are complex interactions between bone-forming osteoblasts and other cells present within the bone microenvironment, particularly vascular endothelial cells that may be pivotal members of a complex interactive communication network in bone. Regenerate bone forms by three modes of ossification, which include intramembranous, enchondral, and transchondroid ossifications, although intramembraneous bone formation is the predominant mechanism of ossification. In this review we discussed the coupling between angiogenesis and mineralization, the biological and mechanical factors affecting them, the cellular and molecular events occurring during distraction osteogenesis, and the emerging modalities to accelerate regenerate bone healing and remodeling.

Animals↗
PubMed2006

Retinopathy of prematurity: two distinct mechanisms that underlie zone 1 and zone 2 disease.

PURPOSE: In its most severe form, retinopathy of prematurity (ROP) is located in posterior retina and affects the smallest, most premature infants. We hypothesize that, depending on whether vasculogenesis (de novo formation of new vessels by transformation of vascular precursor cells (VPCs)) or angiogenesis (budding from existing vessels) is perturbed, it results in significant differences in clinical presentation and therapeutic outcome observed in zone 1 vs zone 2 ROP. DESIGN: The study is a retrospective analysis of the difference in outcome between zones 1 and 2 ROP after cryotherapy and laser therapy. METHODS: A review of the clinical presentation of zones 1 and 2 ROP that correlate this with the topography of formation of human retinal vasculature through vasculogenesis and angiogenesis. RESULTS: Population data on susceptible infants, and outcome statistics of clinical trials are given. Digital images show a correlation between ROP in zone 1 with the region of the retina vascularized through vasculogenesis. CONCLUSION: Zone 1 ROP is correlated with vessel development by vasculogenesis, relative insensitivity to laser/cryotherapy and poorer anatomic and visual outcomes. This suggests that, if the vasculogenic process is perturbed, it results in a distinct clinical presentation, poorer response to therapy, and poorer visual outcome. When the current international classification was developed, knowledge of the processes of human retinal vascular development was incomplete. The work presented here provides a framework for the development of a modification to incorporate these ideas without sacrifice of the essential elements of the international classification of ROP.

Cryotherapy↗
PubMed1995

The role of CXC chemokines as regulators of angiogenesis.

The regulation of angiogenesis is fundamental to a variety of physiological and pathological processes. Although a number of factors have been identified that induce neovascularization, it is becoming increasingly apparent that endogenous angiostatic factors may play an important role in the regulation of angiogenesis during wound repair, chronic inflammation, and growth of solid tumors. In this review, we demonstrate that the CXC chemokine family of cytokines display disparate angiogenic activity depending upon the presence or absence of the ELR motif, a structural amino acid motif previously found to be important in receptor ligand binding on neutrophils. CXC chemokines containing the ELR motif are potent angiogenic factors, inducing both in vitro endothelial chemotaxis and in vivo corneal neovascularization. In contrast, the CXC chemokines that lack the ELR motif, PF4, IP-10, and MIG, not only fail to induce significant in vitro endothelial cell chemotaxis or in vivo corneal neovascularization, but are found to be potent angiostatic factors in the presence of CXC chemokines containing the ELR motif. These findings suggest that the CXC chemokine family can display disparate angiogenic activity that depends upon the presence or absence of the ELR motif. Furthermore, these studies support the notion that the net biological balance in the magnitude of expression of angiogenic and angiostatic CXC chemokines at either the site of wound repair or during tumorigenesis may be important in the regulation of net angiogenesis.

Animals↗
PubMed1996

Shear stress is not sufficient to control growth of vascular networks: a model study.

Local vessel wall shear stress is considered to be important for vessel growth. This study is a theoretical investigation of how this mechanism contributes to the structure of a vascular network. The analyses and simulations were performed on vascular networks of increasing complexity, ranging from single-vessel resistance to large hexagonal networks. These networks were perfused by constant-flow sources, constant-pressure sources, or pressure sources with internal resistances. The mathematical foundation of the local endothelial shear stress and vessel wall adaptation was as follows: delta d/delta t = K*(tau-tau desired)*d, where d is vessel diameter, tau desired is desired shear stress, and K is a growth factor. Single vessels and networks with vessels in series developed stable optimal diameters when perfused at constant flow or with a constant-pressure source with internal resistance. However, when constant-pressure perfusion was applied, these vessels developed ever-increasing diameters or completely regressed. In networks with two vessels in parallel, only one; vessel attained an optimal diameter and the other regressed, irrespective of the nature of the perfusion source. Finally, large hexagonal networks regressed to a single vessel when perfused with a pressure source with internal resistance. The behavior was independent of variation in parameters, although the adaptation rate and the diameter of the final vessel were altered. Similar conclusions hold for models of vascular trees. We conclude that the effect of shear stress on vascular diameter alone does not lead to stable network structures, and additional factor(s) must be present.

Adaptation, Physiological↗
PubMed2004

Inhibition of vascular endothelial growth factor receptor 2-mediated endothelial cell activation by Axl tyrosine kinase receptor.

GAS6, the product of a growth arrest specific (GAS) gene, is the ligand of the tyrosine kinase receptor Axl. GAS6 and Axl are both expressed in endothelial cells, where they are involved in many processes such as leukocyte transmigration through capillaries and neointima formation in injured vessels. Here, we show that Axl stimulation by GAS6 results in inhibition of the ligand-dependent activation of vascular endothelial growth factor (VEGF) receptor 2 and the consequent activation of an angiogenic program in vascular endothelial cells. GAS6 inhibits chemotaxis of endothelial cells stimulated by VEGF-A isoforms, but not that triggered by fibroblast growth factor-2 or hepatocyte growth factor. Furthermore, it inhibits endothelial cell morphogenesis on Matrigel and VEGF-A-dependent vascularization of chick chorion allantoid membrane. GAS6 activates the tyrosine phosphatase SHP-2 (SH2 domain-containing tyrosine phosphatase 2), which is instrumental in the negative feedback exerted by Axl on VEGF-A activities. A dominant-negative SHP-2 mutant, in which Cys 459 is substituted by Ser, reverted the effect of GAS6 on stimulation of VEGF receptor 2 and endothelial chemotaxis triggered by VEGF-A. These studies provide the first demonstration of a cross talk between Axl and VEGF receptor 2 and add new information on the regulation of VEGF-A activities during tissue vascularization.

Animals↗
PubMedDate not supplied

Endothelial progenitor cells: past, state of the art, and future.

Recent evidences suggest that endothelial progenitor cells (EPCs) derived from bone marrow (BM) contribute to de novo vessel formation in adults occurring as physiological and pathological responses. Emerging preclinical trials have shown that EPCs home to sites of neovascularization after ischemic events in limb and myocardium. On the basis of these aspects, EPCs are expected to develop as a key strategy of therapeutic applications for the ischemic organs. Such clinical requirements of EPCs will tentatively accelerate the translational research aiming at the devices to acquire the optimized quality and quantity of EPCs. In this review, we attempt to discuss about biological features of EPCs and speculate on the clinical potential of EPCs for therapeutic neovascularization.

Animals↗
PubMed1998

Role of vascular endothelial growth factor in the response to vessel injury.

In the post-embryonic life, physiological angiogenesis is tightly controlled. Angiogenesis also occurs in pathological circumstances such as tumor vessel proliferation, retinal neovascularization and ischemia. The development of collateral circulation is not only not deleterious, but life saving. Other cases such as neoplastic neovascularization are the basis of the continuous growth of tumors and metastases, and therefore constitute a target of therapeutical efforts. Among a list of molecules able to control angiogenesis, we emphasize the pivotal role of vascular endothelial growth factor (VEGF). VEGF is a potent mitogen for endothelial cells, but is devoid of mitogenic activity for other cell types. VEGF is a polypeptide with four main different isoforms that are remarkably different in terms of solubility and affinity for matrix proteins. VEGF interacts with two endothelial cell-specific tyrosine kinase receptors. The main interest of its study lies in VEGF's role in pathological angiogenic processes, where an increase in the VEGF mRNA expression has been consistently observed. An interesting example is the up-regulation of VEGF's and VEGF receptors' mRNA in a considerable number of human tumors and retina, where they have a critical role in the development of neovascularization. In recent work in our laboratory, we have found further potential interactions of VEGF with pathophysiological mechanisms, namely, the increase in VEGF gene expression under exposure to reactive oxygen species and the positive interaction between VEGF and erythropoietin. VEGF has outstanding possibilities for therapeutic applications aimed at inhibiting or favoring the development of new vessels.

Endothelial Growth Factors↗
PubMed2003

Coordinated interaction of the vascular and nervous systems: from molecule- to cell-based approaches.

Endothelial cells (ECs) build blood vessels and regulate their plasticity in coordination with neurons. Likewise, neurons construct nerves and regulate their circuits in coordination with ECs. Blood vessel/nerve interactions, ultimately, play essential roles for the neurovascular network and brain function. With conventional molecular approaches, such coordinated interaction is likely due to complex interplay of neuroangiogenic factors and receptors. Aside from molecular regulation of neuroangiogenic factors, currently, cell-based approaches to investigate how blood vessels (or nerves) respond to nerves (or blood vessels) appropriately in the pathophysiological situation are gradually emerging. In order to define responsiveness and flexibility of the neurovascular network in response to the local need, the intercellular communication and coordinated interaction between the vascular and nervous systems need to be thought as a working unit. Based on the scale of the working unit which is in the millimeter range with respect to the physical distance of the neurovascular network, we propose to use a rather conceptual term "Millibiology". The millibiological approach for the coordinated interaction might bring us new paradigm to define neurovascular functions in the pathophysiological state.

Adaptation, Physiological↗
PubMed1999

Adaptive angiogenesis in placentas of heavy smokers.

Smoking in pregnancy increases perinatal morbidity and mortality, suggesting impaired placental function, though placental weight is increased. We used scanning electron microscopy to show adaptive angiogenesis in term placental villi from smokers (n=4) and non-smokers (n=4). These images may aid communication of the dangers of smoking in pregnancy.

Adaptation, Physiological↗
PubMed2002

Organogenesis: molecular mechanisms of tubulogenesis.

As organisms have evolved in size and complexity, tubular systems have developed to enable the efficient transport of substances into and out of tissues. These tubular systems are generated using strategies that are based on common elements of cell behaviour, including cell polarization, tube migration to target sites, cell-fate diversification and localization of specialized cells to different regions of the tube system. Using examples from both invertebrate and vertebrate systems, this review highlights progress in understanding these basic principles and briefly discusses the possible evolution of strategies to regulate the morphogenesis of tubular systems.

Animals↗
PubMed2005

Weight loading young chicks inhibits bone elongation and promotes growth plate ossification and vascularization.

The mechanical stimuli resulting from weight loading play an important role in mature bone remodeling. However, the effect of weight loading on the developmental process in young bones is less well understood. In this work, chicks were loaded with bags weighing 10% of their body weight during their rapid growth phase. The increased load reduced the length and diameter of the long bones. The average width of the bag-loaded group's growth plates was 75 +/- 4% that of the controls, and the plates showed increased mineralization. Northern blot analysis, in situ hybridization, and longitudinal cell counting of mechanically loaded growth plates showed narrowed expression zones of collagen types II and X compared with controls, with no differences between the relative proportions of those areas. An increase in osteopontin (OPN) expression with loading was most pronounced at the bone-cartilage interface. This extended expression overlapped with tartarate-resistant acid phosphatase staining and with the front of the mineralized matrix in the chondro-osseous junction. Moreover, weight loading enhanced the penetration of blood vessels into the growth plates and enhanced the gene expression of the matrix metalloproteinases MMP9 and MMP13 in those growth plates. On the basis of these results, we speculate that the mechanical strain on the chondrocytes in the growth plate causes overexpression of OPN, MMP9, and MMP13. The MMPs enable penetration of the blood vessels, which carry osteoclasts and osteoblasts. OPN recruits the osteoclasts to the cartilage-bone border, thus accelerating cartilage resorption in this zone and subsequent ossification which, in turn, contributes to the observed phenotype of narrower growth plate and shorter bones.

Adaptation, Physiological↗
PubMed2006

The vasohibin family: a negative regulatory system of angiogenesis genetically programmed in endothelial cells.

Biological phenomena are under the precise control by the genome. For the regulation of angiogenesis, proangiogenic genes such as VEGFs and angiopoietins are highly conserved, act specifically on endothelial cells, and play a fundamental role. In this sense, nature should prepare specific antiangiogenic genes as well. However, this counterpart of genomic regulation of angiogenesis remains to be established. We recently isolated a novel endothelium-derived angiogenesis inhibitor and named it vasohibin. Vasohibin is dominantly expressed in endothelial cells, induced by the stimulation with VEGF or FGF-2, and selectively affects on endothelial cells and inhibits angiogenesis. Although the mechanism of how vasohibin inhibits angiogenesis remains to be elucidated, our discovery of vasohibin as an endothelium-derived VEGF-inducible angiogenesis inhibitor should shed light on the genomic basis of the negative regulation of angiogenesis.

Alternative Splicing↗
PubMed2004

Development and pathology of the hyaloid, choroidal and retinal vasculature.

During embryogenesis, the development and differentiation of the eye requires the concomitant formation of the neural/glial elements along with a dense vascular network. The adult neural retina is supported by two distinct vascular systems, the proper retinal vessels and the choroidal vessels. The two beds differ not only in their pattern of embryonic differentiation, but also in their function in the adult organism. The retinal vasculature has barrier properties similar to those observed in the brain, whereas the choroidal vessels display a highly fenestrated phenotype. The hyaloid vasculature is a transient embryonic vascular bed which is complete at birth in mammals and regresses contemporaneously with the formation of the retinal vasculature. The dependence of the retina on its blood supply makes it highly vulnerable to any vascular changes and indeed ocular diseases, such as proliferative retinopathy, age-related macular degeneration and the hyperplastic primary vitreous, which are associated with abnormalities of the different vascular beds of the eye. A number of factors have been implicated in developmental and pathological changes in vessel formation and regression, including fibroblast growth factors, platelet-derived endothelial growth factor and vascular endothelial growth factor, among others. The purpose of this review is to describe and discuss new insights into the mechanisms and molecular cues involved in the development of the normal and pathological vascular systems of the eye. The characterization of the molecules and cell-cell interactions involved in the formation, stabilization and regression of new vessels has led to the identification of potential control points for therapeutic intervention.

Animals↗
PubMed1999

[Vascular endothelial factor (VEGF): therapeutic angiogenesis and vasculogenesis in the treatment of cardiovascular disease].

The formation of new blood vessel is essential for a variety of physiological processes like embryogenesis and the female reproduction as well as pathological processes like tumor growth, wound healing and neovascularization of ischemic tissue. Vasculogenesis and angiogenesis are the mechanisms responsible for the development of the blood vessels. While angiogenesis refers to the formation of capillaries from pre-existing vessels in the embryo and adult organism, vasculogenesis, the development of new blood vessels from in situ differentiating endothelial cells, has been previously considered restricted to embryogenesis. Recent investigations, however, show the existence of endothelial progenitor cells (EPCs) in the peripheral blood of the adult and their participation in ongoing neovascularization. Molecular and cell-biological experiments suggest that different cytokines and growth factors have a stimulatory effect on these bone-marrow derived EPCs. Results with GM-CSF (granulocyte macrophage-colony stimulating factor) and VEGF (vascular endothelial growth factor) open a new insight into the clinical use of cytokines and in particular the use of growth factors in gene therapy. The administration via protein or plasmid-DNA for neovascularization seems to enhance both pathways, angiogenesis and vasculogenesis.

Cardiovascular Diseases↗
PubMed2004

PEDF derived from glial Müller cells: a possible regulator of retinal angiogenesis.

A precise balance between stimulators and inhibitors of angiogenesis, such as vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF), respectively, is essential for angiogenic homeostasis in ocular tissues. Retinal hypoxia is accompanied by some pathological conditions that may promote intraocular neovascularization. Here we demonstrate that retinal glial (Müller) cells express and release pigment epithelium-derived factor (PEDF). Decreasing oxygen concentrations cause strong attenuation of PEDF release resulting in enhanced VEGF/PEDF ratios. Exposure of Müller cells to VEGF suppressed PEDF release in a dose-dependent manner. This may represent a novel mechanism of ocular angiogenic homeostasis sufficient in the control of PEDF levels during normoxia or mild hypoxia but supplemented by other (hitherto unknown) mechanisms in cases of strong hypoxia. In spite of the enhanced VEGF/PEDF ratios resulting from hypoxia, conditioned media of Müller cells failed to stimulate additional proliferation of retinal endothelial cells. These findings suggest that in the ischemic retina, Müller cells generate a permissive condition for angiogenesis by secreting more VEGF and less PEDF, but the onset of retinal endothelial cell proliferation requires another triggering signal that remains to be identified.

Animals↗