Development Of New Capillaries Research Articles

MORPHOLOGICAL CHARACTERISTICS OF THE ANTERIOR ABDOMINAL WALL TIS-SUES IN CASES OF IMPLANTATION OF POLYPROPYLENE MESH WITH PRF MEMBRANE

According to the experimental study on Vietnamese pigs after implantation of a polypropylene mesh with PRF membrane into retromuscular space, the results of ultrastructural changes in the cells of muscular aponeurotic layer of abdominal wall were presented. It was proved that on the 14th day of the experiment, inflammatory changes in tissues were expressed significantly less than in cases of the isolated implantation of the polypropylene mesh without PRF membrane. Activation of fibroblasts and signs of fiber structures development around the mesh material increased. In the late experimental period (28 days), at the microscopic and electron-microscopic levels the minor manifestations of inflammatory reaction, improved microcirculation in the area of implantation of the mesh with PRF membrane were found that in turn contributed to the increased activity of fibroblasts and development of collagen fibers around the mesh material. The use of PRF plasma membranes stimulated an active development of new capillaries, improved blood flow, accelerated metabolic processes in tissues, and suddenly increased development of collagen, hyaluronic acid that in turn created favourable environment for a complete integration of the polypropylene mesh into the muscular aponeurotic layer of anterior abdominal wall tissue.

Growth Factors in the Pathogenesis of Retinal Neurodegeneration in Diabetes Mellitus.

Neurodegeneration is an initial process in the development of diabetic retinopathy (DR).High quantities of glutamate, oxidative stress, induction of the renin-angiotensin system (RAS) and elevated levels of RAGE are crucial elements in the retinal neurodegeneration caused by diabetes mellitus. At least, there is emerging proof to indicate that the equilibrium between the neurotoxic and neuroprotective components will affect the state of the retinal neurons.Somatostatin (SST), pigment epithelium-derived factor (PEDF), and erythropoietin (Epo) are endogenous neuroprotective peptides that are decreased in the eye of diabetic persons and play an essential role in retinal homeostasis. On the other hand, insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF) are pivotal proteins which participate in the development of new capillaries and finally cause damage to the retinal neurons. During recent years, our knowledge about the function of growth factors in the pathogenesis of retinal neurodegeneration has increased. However, intensive investigations are needed to clarify the basic processes that contribute to retinal neurodegeneration and its association with damage to the capillary blood vessels. The objective of this review article is to show new insights on the role of neurotransmitters and growth factors in the pathogenesis of diabetic retinopathy. The information contained in this manuscript may provide the basis for novel strategies based on the factors of neurodegeneration to diagnose, prevent and treat DR in its earliest phases.

Botulinum Toxin A Upregulates Rac1, Cdc42, and RhoA Gene Expression in a Dose-Dependent Manner: In Vivo and in Vitro Study.

Angiogenesis is the development of new capillaries from existing blood vessels and is a prerequisite for the wound-healing process. Many lines of scientific evidences have shown that complicated roles of small guanosine triphosphatases (GTPases) (ras-related C3 botulinum toxin substrate 1 [Rac1], cell division control protein 42 [Cdc42], and ras homolog gene family, member A [RhoA]) in regulation of signal transduction pathways exist to transmit distinct cellular effects on the modulation of actin cytoskeleton remodeling such as cell cycle progression, cell survival, and cell motility. In addition, these small GTPases activate mitogen-activated protein kinase kinase kinases (MAP3Ks) leading to activated mitogen-activated protein kinase kinases (MAPKK), mitogen-activated protein kinase (MAPK), and various transcription factors such as vascular endothelial growth factor with involvement of MAPK signaling pathways.In this study, the authors hypothesized that botulinum toxin A increases angiogenesis via the expression of small GTPases in vivo and in vitro studies.In vivo experiment, 24 Sprague-Dawley rats were randomly divided into 2 groups: a control group and a botulinum toxin A group. Five days prior to superiorly based transverse rectus abdominis myocutaneous flap elevation, the botulinum toxin A (BoTA) group was pretreated with BoTA, while the control group was pretreated with normal saline. quantitative real-time polymerase chain reaction was performed to evaluate the expression of Rac1, RhoA, and Cdc42.The angiogenic effects of botulinum toxin A on human dermal fibroblasts were measured in vitro experiment. To understand the mechanism of botulinum toxin A on small GTPases production of fibroblasts, Rac1, Cdc42, and RhoA were measured using qRT-PCR.The relative messenger ribonucleic acid expression of Rac1, RhoA, and Cdc42 was significantly higher in the BoTA group than in the control group, in every zone and pedicle muscle, on postoperative days 1, 3, and 5. Levels of these molecules increased significantly in human dermal fibroblasts grown in the presence of BoTA compared with control group over 5 IU.Our in vivo and in vitro studies suggest that administration of BoTA upregulates the expression of RhoA, Rac1, and Cdc42 in a dose-dependent manner. MAPK signaling pathway might be involved in BoTA-induced angiogenesis mechanism. N/A.

Angiogenesis in The Ovary - The Most Important Regulatory Event for Follicle and Corpus Luteum Development and Function in Cow - An Overview.

In the ovary, the development of new capillaries from pre-existing ones (angiogenesis) is a complex event regulated by numerous local factors. The dominant regulators of angiogenesis in ovarian follicles and corpora lutea are the vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), insulin-like growth factor (IGF), angiopoietin (ANPT) and hypoxia-inducible factor (HIF) family members. Antral follicles in our study were classified according to the oestradiol-17-beta (E2) content in follicular fluid (FF) and were divided into five classes (E2 < 0.5, 0.5-5, 5-20, 20-180 and >180 ng/ml FF). The corresponding sizes of follicles were 5-7, 8-10, 10-13, 12-14 and >14 mm, respectively. Follicle tissue was separated in theca interna (TI) and granulosa cells (GC). The corpora lutea (CL) in our study were assigned to the following stages: days 1-2, 3-4, 5-7, 8-12 13-16 and >18 of the oestrous cycle and months 1-2, 3-4, 6-7 and >8 of pregnancy. The dominant regulators were measured at mRNA and protein expression levels; mRNA was quantified by RT-qPCR, hormone concentrations by RIA or EIA and their localization by immunohistochemistry. The highest expression for VEGF-A, FGF-2, IGF-1 and IGF-2, ANPT-2/ANPT-1 and HIF-1-alpha was found during final follicle maturation and in CL during the early luteal phase (days 1-4) followed by a lower plateau afterwards. The results suggest the importance of these factors for angiogenesis and maintenance of capillary structures for final follicle maturation, CL development and function.

Epalrestat induces cell proliferation and migration in endothelial cells via mTOR activation through PI3/Akt signaling

Angiogenesis is a major physiological response to ischemia that involves development of new capillaries and collateral circulation from preexisting vessels, and endothelial cell (EC) proliferation and migration are crucial events for this process. Epalrestat, an aldose reductase inhibitor, is used as a therapeutic agent for the treatment of diabetic peripheral neuropathy. We examined the effect of epalrestat on the proliferation and migration of a mouse microvascular endothelial cell line (bEnd3 cells) measured by scratch wound assay and cell proliferation assay. Epalrestat significantly enhanced the proliferation and migration of bEnd3 cells. The addition of epalrestat resulted in the phosphorylation of Akt and p70 S6 kinase (p70S6K), and this effect was attenuated by LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K). Rapamycin, a specific inhibitor of the mammalian target of rapamycin (mTOR), inhibited p70S6K phosphorylation only. Both rapamycin and LY294002 inhibited epalrestat-induced proliferation and migration. These data suggest that epalrestat may activate PI3/Akt/mTOR signaling and that this pathway contributes to the proliferation and migration of EC.

Modulation of angiogenesis by dietary phytoconstituents in the prevention and intervention of breast cancer

Breast cancer is the leading cause of cancer-related deaths for women in the United States and the rest of the world. About 8% of women develop breast cancer during the course of their lives. Dietary habits are closely associated with both the risk and progression of breast cancer. Dietary agents have accumulated increasing importance with regards to the prevention and treatment of breast cancer. One such manner by which these compounds can target breast cancer development and progression is through interference with the angiogenic pathways. Angiogenesis is an intricate process that involves the development of new capillaries from previously existing blood vessels. Disruption of this pathway, therefore, provides a novel and effective avenue for therapeutic intervention of breast cancer. Various phytochemicals found in the diet kill breast cancer cells in vitro and prevent as well as suppress breast cancer progression in various preclinical animal models. This review examines the value of dietary phytoconstituents in the prevention and treatment of breast cancer through modulation of the intricate and complex process of angiogenesis. In addition, the potential benefits, challenges, and future directions of research on anti-angiogenic dietary phytochemicals in the prevention and intervention of breast cancer are also addressed.

Nitric Oxide-Donating Derivatives of Chrysin Stimulate Angiogenesis and Upregulating VEGF Production

Angiogenesis, the development of new capillaries from pre-existing vessels, requires the coordinate activation of endothelial cells, which migrate and proliferate to form functional vessels. Endothelial dysfunction and decreased nitric oxide bioavailability may underscore the impairment of angiogenesis. As such, the delivery of exogenous NO is an attractive therapeutic option that has been used to therapeutic angiogenesis. In this paper, a novel group of hybrid nitric oxide-releasing chrysin derivatives was synthesized. The results indicated that all these chrysin derivatives exhibited promotion of endothelial migration and tubulogenesis in vitro as well as stimulation angiogenesis in vivo.Furthermore, all compounds released NO upon incubation with phosphate buffer at pH 7.4 and enhanced VEGF secretion and VEGF mRNA expression of endothelial cells. These hybrid ester NO donor prodrugs offer a potential drug design concept for the development of therapeutic or preventive agents for angiogenesis deficiency due to ischemic diseases.

Targeting Angiogenesis in Rheumatoid Arthritis

Angiogenesis, the development of new capillaries, is a crucial process in health and disease. The perpetuation of neovascularization in rheumatoid arthritis is highly involved in leukocyte extravasation into the synovium and pannus formation. Numerous soluble and cell surface-bound angiogenic mediators, including growth factors, cytokines, proteases, matrix macromolecules, cell adhesion receptors, chemokines and chemokine receptors, have been implicated in the process of neovascularization. Endogenous angiostatic factors, primarily angiostatin, endostatin, IL-4, IL-13, some angiostatic chemokines may be used to downregulate neovascularization. In addition, angiogenesis might be targeted by several specific approaches against VEGF, angiopoietin, α(v)β(3) integrin or by exogenously administered compounds including DMARDs, anti-TNF agents, fumagillin analogues or thalidomide. Potentially all anti-angiogenic could be tried in order to control synovitis.

Influence of triamcinolone intravitreal injection on retinochoroidal healing processes

To analyze the effects of triamcinolone intravitreal injection on the wound healing processes after argon laser retinal photocoagulation, wild type C57BL/6J mice, 8–12 weeks old underwent a standard argon laser photocoagulation protocol. After pentobarbital anesthesia and pupil dilatation, argon laser lesions were induced (50 μm, 400 mW, 0.05 s). Two photocoagulation impacts created two disc diameters from the optic nerve in both eyes. The photocoagulated mice were divided into four groups: Group I ( n = 12), photocoagulation controls, did not receive any intravitreous injection. Group II ( n = 12), received an intravitreous injection of 1 μl of balanced salt solution (BSS). Group III ( n = 12), received an intravitreous injection of 1 μl containing 15 μg of triamcinolone acetonide (TAAC) in BSS. Two mice from each of these three groups were sacrificed at 1, 3, 7, 14 days and 2 and 4 months after photocoagulation. Group IV ( n = 10) received 1.5, 3, 7.5, 15, or 30 μg of TAAC and were all sacrificed on day 14. The enucleated eyes were subjected to systematic analysis of the cellular remodeling processes taking place within the laser lesion and its vicinity. To this purpose, specific antibodies against GFAP, von Willebrand factor, F4/80 and KI67 were used for the detection of astrocytes, activated Müller cells, vascular endothelial cells, infiltrating inflammatory cells and actively proliferating cells. TUNEL reaction was also carried out along with nuclear DAPI staining. Temporal and spatial observations of the created photocoagulation lesions demonstrate that 24 h following the argon laser beam, a localized and well-delineated affection of the RPE cells and choroid is observed in mice in Groups I and II. The inner retinal layers in these mice eyes are preserved while TUNEL positive (apoptotic) cells are observed at the retinal outer nuclear layer level. At this stage, intense staining with GFAP is associated with activated retinal astrocytes and Müller cells throughout the laser path. From day 3 after photocoagulation, dilated new choroidal capillaries are detected on the edges of the laser lesion. These processes are accompanied by infiltration of inflammatory cells and the presence of proliferating cells within the lesion site. Mice in Group III treated with 15 μg/μl of triamcinolone showed a decreased number of infiltrating inflammatory cells and proliferating cells, which was not statistically significant compared to uninjected laser treated controls. The development of new choroidal capillaries on the edges of the laser lesion was also inhibited during the first 2 months after photocoagulation. However, on month 4 the growth of new vessels was observed in these mice treated with TAAC. Mice of Group IV did not show any development of new capillaries even with small doses. After argon laser photocoagulation of the mouse eye, intravitreal injection of triamcinolone markedly influenced the retina and choroid remodeling and healing processes. Triamcinolone is a powerful inhibitor of the formation of neovessels in this model. However, this inhibition is transient. These observations should provide a practical insight for the mode of TAAC use in patients with wet AMD.

Effect of a Statin on an In Vitro Model of Endometriosis

Effect of a Statin on an In Vitro Model of Endometriosis

Exercise-induced Gene Expression Of Angiogenesis-regulated Transcriptional Factors Differs Between Fiber Types In The Skeletal Muscle

Exercise training promotes many adaptations in skeletal muscle, including the development of new capillaries, known as angiogenesis. Acute exercise induces a greater expression of genes known to promote angiogenesis, such as vascular endothelial growth factor (VEGF). The exercise-induced alteration of VEGF gene expression differs between muscle fiber types (i.e., slow-twitch oxidative muscle fibers and fast-twitch glycolytic muscle fibers). PURPOSE To gain insight into the molecular mechanism underlying the difference of exercise-induced angiogenesis between slow fiber type and fast fiber type, we investigated whether the basal and exercise-induced gene expression of angiogenesis-regulated transcriptional factors in muscle differ between these two fiber types. METHODS We determined a difference of level in gene expression of angiogenesis-regulated transcriptional factors (transforming growth factor [TGF]-beta1, c-Jun and c-Fos) between the muscle of slow fiber type (soleus) and fast fiber type (plantaris) at rest and the end of a single bout of exercise (running on a treadmill for 30-min) using male Sprague-Dawley rats (10 wk old). RESULTS The mRNA expression of TGF-beta1, c-Jun and c-Fos at resting condition was significantly higher in the soleus than the plantaris. On the other hand, the mRNA expressions of TGF-beta1 and c-Jun in the plantaris, but not in the soleus, were significantly increased by exercise. The exercise-induced increase in c-Fos mRNA expression was higher in the plantaris than the soleus, although the mRNA expressions of c-Fos in both muscles were significantly increased by exercise. Thus, slow type fiber constitutively activates transcriptional regulation of angiogenesis at resting condition, whereas the exercise-induced increase in gene expression of angiogenesis-regulated transcriptional factors mainly occurs in fast fiber type of muscle. CONCLUSION The present study suggests that 1) the difference of constitutive gene expression of angiogenesis-regulated transcriptional factors between fast and slow fiber types of muscle may be one of the causal factors for the difference in homeostatic angiogenesis to the muscle capillary and 2) the exercise-induced different manner of gene expression of angiogenesis-regulated transcriptional factors between fast and slow fiber types of muscle may participate in molecular mechanism underlying exercise-enhanced angiogenesis. Supported by grants from the Ministry of Education, Science, Sports and Culture of Japan (15650130, 16500391).

Angiogenese im Corpus luteum des menstruellen Zyklus und der Frühgravidität

Die Entwicklung eines normalen Gefäßsystems ist eine Voraussetzung für die Funktionsfähigkeit von Organen, da nur über die Blutbahn die Zellen mit Nährstoffen und Sauerstoff versorgt werden. Unter Vaskulogenese versteht man die Entwicklung der großen Stammgefäße im Organismus, die nur während der Embryonalperiode vorkommt, während Angiogenese als die Entwicklung neuer, abzweigender Kapillaren aus vorbestehenden Stammgefäßen definiert wird. Angiogenese findet auch später im ausgewachsenen Organismus vor allem bei Pathologien (Tumorangiogenese, Wundheilung, diabetische Retinopathie, Endometriose) statt. Ansonsten sind die meisten Organgefäßsysteme des Erwachsenen ausgereift, so dass aktive Angiogenese nicht mehr benötigt wird. Eine Ausnahme ist der weibliche Reproduktionstrakt. Als Besonderheit findet hier Angiogenese in monatlichen Zyklen statt, so dass eine übergeordnete hormonelle Kontrolle anzunehmen ist. Die Angiogenese und deren Regulation lassen sich vor allem während der Corpus-luteum-Entwicklung untersuchen, da hier innerhalb weniger Tage ein Organgefäßsystem entsteht, das eine hohe Durchblutung gewährleistet, so dass das Corpus luteum zu den am besten durchbluteten Organen des Organismus gehört. Der Blutfluss im Corpus luteum lässt sich mit malignen Tumoren vergleichen. Dieser Übersichtsartikel beschreibt die Physiologie der angiogenetischen Vorgänge im Corpus luteum und diskutiert die molekularen und hormonellen Regulationsmechanismen mit besonderem Schwerpunkt während der Frühgravidität.

Role of nitric oxide in the modulation of angiogenesis.

Angiogenesis, the development of new capillaries form pre-existing vessels, requires the coordinate activation of endothelial cells, which migrate and proliferate in response to growth factors to form functional vessels. Therapeutic angiogenesis is proposed to restore tissue integrity and function following damage and ischemia, while strategies aimed to block or suppress the neovascular growth are designed as adjuvant therapies for cancer treatment. Different experimental and clinical observations support the existence of a molecular/biochemical link between vasodilation, nitric oxide (NO) production and angiogenesis. NO significantly contributes to the prosurvival/proangiogenic program of capillary endothelium by triggering cell growth and differentiation via endothelial-constitutive NO synthase (ecNOS) activation, and cyclic GMP (cGMP) dependent gene transcription. Re-establishment of a balanced NO production in the cardiovascular system results in a reduction of cell damage during inflammatory and vascular diseases. Elevation of NOS activity in correlation with angiogenesis and tumor growth and aggressiveness has been extensively reported in experimental and human tumors. On these bases, the nitric oxide pathway appears to be a promising target for the development of pro- and anti-angiogenic therapeutic strategies. In particular, the use of NOS inhibitors or NO scavengers seems appropriate to reduce edema, block angiogenesis and facilitate antitumor drug delivery.

Pyogenic granuloma following oculoplastic procedures: An imbalance in angiogenesis regulation?

Background: Pyogenic granuloma is a vasoproliferative inflammatory response composed of granulation tissue. The pathogenesis is not entirely clear. We describe a series of patients with pyogenic granulomas occurring following common oculoplastic procedures and propose a common etiology.Methods: Sixteen cases of pyogenic granuloma that occurred after various oculoplastic procedures from 1991 to 2000 were collected from the files of two oculoplastic surgeons.Results: Pyogenic granulomas were found to occur at surgical and nonsurgical sites associated with tissue irritation or inflammation or both.Interpretation: Capillaries are a predominant component of wound healing and pyogenic granulomas. The growth and development of new capillaries follows an orderly sequence of events that is highly regulated by a variety of angiogenic factors. We postulate an imbalance in angiogenesis regulation as the common pathway for pyogenic granuloma development.

Transmyocardial channeling

Transmyocardial channeling

Angiogenesis in Mesotheliomas: Role of Mesothelial Cell Derived IL-8

Interleukin-8 (IL-8) has been described as an important angiogenic factor causing proliferation and chemotaxis of endothelial cells in vitro and the development of new capillaries in vivo. Importantly, several tumors have been shown to produce IL-8, which allows for local tumor growth and invasion. Pleural mesothelioma is characterized by local tumor extension and invasion of surrounding tissue, with distant metastasis being rare. We hypothesized that pleural mesotheliomas produce IL-8 as a mechanism for angiogenesis, with subsequent extension and propagation of the tumor.

Cytokine regulation of angiogenesis in breast cancer: the role of tumor-associated macrophages.

Studies over the past 20 years have established that the development of new capillaries from an existing vascular network (a process called angiogenesis) is an essential component of tumor growth. Malignant tumors do not grow beyond 2-3 mm3 in size unless they stimulate the formation of new blood vessels and thus provide a route for the increased inflow of nutrients and oxygen and outflow of waste products. Tumor angiogenesis also provides an essential exit route for metastasizing tumor cells from the tumor to the bloodstream. Indeed, extensive neovascularization is a poor prognostic factor in several forms of human cancer. Angiogenesis is a complex, multistep process driven by many local signals within the tumor. This involves the degradation of the extracellular matrix around a local venule after the release of collagenases and proteases, the proliferation and migration of capillary endothelial cells, and their differentiation into functioning capillaries. Cytokines produced by various cell types present within the microenvironment of solid tumors form a complex, dynamic network in which they have multiple effects on tumor progression. Herein we review our work on the presence, and possible regulatory influence on tumor angiogenesis, of a number of these cytokines within invasive breast carcinomas. We have combined immunocytochemistry with a single cell cytokine release assay called the reverse hemolytic plaque assay to investigate the cellular sources of the key angiogenic cytokines, vascular endothelial growth factor, basic fibroblast growth factor, and tumor necrosis factor-alpha. Tumor-associated macrophages in the stromal compartment of these tumors and/or malignant epithelial cells were seen to be a major producer cell for these cytokines, whereas tumor necrosis factor-alpha receptors were expressed by leukocytes, malignant cells, and endothelial cells in tumor blood vessels.

Red muscle fibre and capillary dimensions in different sizes of a tilapia, Oreochromis niloticus (Trewavas)

Measurements of muscle dimensions that affect respiration in relation to body weight were carried out in a tilapia, Oreochromis niloticus. The fish used in all measurements weighed 0.65–812.3 g. The data were analysed with respect to body weight using logarithmic transformations (log Y=log a+blog W). The slopes (b) of the log/log regression lines for weight of body trunk red muscle, average cross-sectional area of muscle fibre, average number of capillaries in direct contact with a muscle fibre, average capillary contact length with a fibre as a fraction of average fibre circumference and number of capillaries mm2 of fibre cross-sectional area [NA(cƒ)] were 1.16, 0.221, 0.084, 0.015, and −0.137 respectively. These results show that there is an increase in muscle cross-sectional fibre area and number of capillaries in contact with muscle fibres whereas number of capillaries supplying a unit area of muscle fibre decreases during development. There is development of new capillaries with increase in cross-sectional area of red muscle fibres.

Endothelial cell migration and chemotaxis in angiogenesis.

Our goal has been to provide a quantitative analysis of the random motility and chemotaxis of microvessel endothelial cells (MEC) in order to understand the role of these functions in the development of new capillaries. A major difference of our work from previous investigations has been our use of mathematical analysis to interpret experimental results, and to relate in vitro migration measurements to in vivo angiogenesis observations. In this paper we present some of our methods and their rationale, with recent results from both experiment and mathematical models.

An in vitro model of cell migration: Evaluation of vascular endothelial cell migration

In vivo vascular endothelial cell (VEC) migration is thought to play a central role in the development of new capillaries as well as the resurfacing of large vessels. Recently, we have developed an in vitro VEC migration assay system based on the ability of VEC to migrate off of tissue culture microcarrier beads. For these studies, bovine pulmonary artery VEC were grown to confluence on Cytodex 3 microcarrier beads (MCB). Next, the confluent VEC covered microcarrier beads were pipetted into 4-cm 2 wells of a tissue culture plate and incubated at 37° C 5% CO 2 . At various time intervals, the movement of the VEC off of the MCB onto the tissue culture surface was evaluated microscopically. Using this assay, we have studied the effect of endothelial cell growth supplement and various matrices (i.e., fibronectin, gelatin, and Matrigel) on VEC migration. These studies demonstrated that: (i) gelatin had no effect on normal or mitomycin C-pretreated VEC migration; (ii) fibronectin had no effect on normal VEC migration, but stimulated the relative migration of mitomycin pretreated VEC; and (iii) Matrigel significantly suppressed both normal and mitomycin C-pretreated VEC migration. Endothelial cell growth supplement (ECGS) stimulated both normal and mitomycin C-pretreated VEC migration on fibronectin at concentrations of 10 μg/ml ECGS. Pretreatment with ECGS had no effect of normal or mitomycin C VEC migration on gelatin. Finally, ECGS stimulated a statistically significant increase in the migration of normal and mitomycin C-pretreated VEC migration on Matrigel. Thus, these data clearly demonstrate the ability of the MCB assay to detect both enhancements and suppressions of VEC migration in vitro, and therefore this new method should prove a simple and rapid method for the quantitation of VEC migration in vitro.