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Results for “Neovascularization, Pathologic”

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PubMed1992

Mast cells and angiogenesis.

Much data exists in the literature to suggest a correlation between mast cell accumulation and angiogenesis. This correlation exists for normal blood vessel growth as well as pathological vessel growth. The recruitment of mast cells to sites of angiogenesis is not completely understood. However, once at the site, mast cell products may act directly on endothelial cells to stimulate their migration and/or proliferation or may act indirectly by degrading connective tissue matrix to provide space for neovascular sprouts to form. Understanding the role of mast cells in angiogenesis may provide avenues for intervening in and manipulating the neovascularization process.

Animals↗

PubMed1994

The endogenous oestrogen metabolite 2-methoxyoestradiol inhibits angiogenesis and suppresses tumour growth.

The formation of new blood vessels (angiogenesis) is critical for the growth of tumours and is a dominant feature in various angiogenic diseases such as diabetic retinopathy, arthritis, haemangiomas and psoriasis. Recognition of the potential therapeutic benefits of controlling pathological angiogenesis has led to a search for angiogenesis inhibitors. Here we report that 2-methoxyoestradiol, an endogenous oestrogen metabolite of previously unknown function, is a potent inhibitor of endothelial cell proliferation and migration as well as angiogenesis in vitro. Moreover, when administered orally in mice, it strongly inhibits the neovascularization of solid tumors and suppresses their growth. Unlike the angiostatic steroids of corticoid structure, it does not require the co-administration of heparin or sulphated cyclodextrins for activity. Thus, 2-methoxyoestradiol is the first steroid to have high antiangiogenic activity by itself. Our results suggest that this compound may have therapeutic potential in cancer and other angiogenic diseases.

2-Methoxyestradiol↗

PubMed1990

Subretinal hemorrhages with or without choroidal neovascularization in the maculas of patients with pathologic myopia.

We examined 20 patients (24 eyes) who had refractive errors of -8 diopters or more and subretinal hemorrhages at the initial visit. They were divided into two groups according to fluorescein angiographic findings: 15 eyes without choroidal neovascularization (CNV) and 9 eyes with CNV. Subretinal hemorrhage without CNV was frequent in patients aged 20-39 years (mean, 36.8 years). CNV was common in patients aged 60-79 years (mean, 61.0 years). No relationship was noted between refractive error and type of hemorrhage. In the eyes without CNV, the subretinal hemorrhages disappeared spontaneously after a few months. The visual acuity of these patients was variable at the initial visit (range, 0.01-0.8), and was unchanged or improved during the follow-up period. In the eyes with CNV, the visual acuity was less than 0.1 at the initial visit and was unchanged or worse during the follow-up period.

Adult↗

PubMed1995

Fibroblast growth factors: at the heart of angiogenesis.

Acidic fibroblast growth factor (FGF-1) and basic fibroblast growth factor (FGF-2) are ubiquitous cytokines found in many tissues. They have effects on multiple cell types derived from mesoderm and neuroectoderm, including endothelial cells. In this review the structure and function of the fibroblast growth factor family and its receptors are described. The evidence implicating both FGF-1 and FGF-2 in the control of blood vessel formation is presented and their involvement in normal and pathological angiogenesis during adult life is then described in more detail.

Adult↗

PubMed1994

Normal and abnormal development of the blood-brain barrier.

The blood-brain barrier is responsible for the maintenance of the neuronal microenvironment. This is accomplished by isolation of the brain from the blood by the tight junctions that join endothelial cells in cerebral microvessels, and by selective transport and metabolism of substances from blood or brain by the endothelial cells. This review describes the growth and maturation of the brain vasculature, and the development of the special properties of the endothelia at the blood-brain interface. Evidence suggests that the development of the unique properties of the brain microvasculature is a consequence of tissue-specific interactions between endothelial cells of extraneural origin and developing brain cells. The cellular and molecular mechanisms that control these processes are as yet unknown but this review will include experimental studies which have used in vivo and in vitro systems to investigate what factors may be involved, and some pathological conditions in which abnormal barrier development is thought to be an important aspect of the disease process.

Animals↗

PubMed1981

[Biology of the femoral head necrosis. Clinical studies (author's transl)].

From the study of femoral heads either experimental or human it is clear that the clinico-pathological called idiopathic necrosis is due to the death of bone cells, as it is in necrosis after fracture or dislocation. But the cause of cell's death is clearly avascular only in traumatic necrosis: in idiopathic necrosis there is no evidence of arterial alteration or obliteration, whatever condition is associated. In both avascular (traumatic) necrosis, and idiopathic necrosis, the cartilage remains alive: the deformation of the head, secondary rupture and destruction of cartilage and finally osteoarthritis are the consequence not of the death of bone cells (a dead head with living cartilage would work for along time) but of the revascularisation process. This process is different in the two syndrome. In idiopathic necrosis proliferation of living tissues in the head is active, but bone formation is limited, shearing forces create a subchondral fracture in the dead part of the head. In avascular necrosis, after the fracture is united, proliferation invades the dead head, with active osteogenesis. The pathological fracture is between dead and bone and revascularised part of the head. One can suggest as therapeutic measure the prevention of revascularisation.

Cell Survival↗

PubMedDate not supplied

Isolated capillary proliferation in Leigh's syndrome.

An infant with hypotonia and recurrent apneic spells died with a diagnosis of pyruvate dehydrogenase deficiency and showed typical pathological changes of Leigh's syndrome at postmortem. Despite the prominence of symptoms suggesting dysfunction of brainstem respiratory centers during life, lesions were not found in the upper medulla. However, quantitative morphometric analysis demonstrated abnormal capillary hyperplasia in the region including and between the nucleus ambiguus and nucleus tractus solitarius. There was an average area of 8.0 +/- 2.5 x 10(6) mm2 occupied by capillaries per 0.75 mm2 field in the patient's brainstem, compared with 4.6 +/- 1.6 x 10(6) mm2 and 5.5 +/- 1.4 x 10(6) mm2 in two age-matched controls (p < 0.01). We speculate that capillary hyperplasia is a pathological marker of chronically impaired oxidative metabolism in the central nervous system in metabolic disease.

Brain↗

PubMed1994

Transforming growth factor-beta 1 mediates mast cell chemotaxis.

It remains unknown which factor(s) control mast cell recruitment in chronic immune reactions. Although TGF-beta has been shown to function as a potent chemotactic factor for monocytes, fibroblasts, and neutrophils, its effect on mast cells has not been previously determined. In this study, TGF-beta 1 was shown to cause directed migration of cultured mouse mast cells at femtomolar concentrations, with a maximal chemotactic response observed at 25 fM. Moreover, chemotaxis to TGF-beta was also seen using freshly isolated rat peritoneal mast cells. Addition of neutralizing Ab to TGF-beta abrogated its chemotactic activity for both freshly isolated rat peritoneal mast cells and cultured mouse mast cells, whereas an irrelevant species-matched control Ab had no effect. Checkerboard analysis confirmed the mast cell chemotactic activity after exposure to concentration gradients of TGF-beta. Mast cells were observed to undergo rapid and extensive shape changes on exposure to TGF-beta, assuming a polarized morphology in preparation for migration. Other known mast cell chemoattractants including laminin, c-kit ligand, and IL-3 were found to be considerably less potent on a molar basis in inducing directed migration. Affinity cross-linking studies identified TGF-beta binding proteins with M(r) at 70 and 288 kDa, consistent with types I and III TGF-beta receptors on the mast cells. In summary, TGF-beta is the most potent chemoattractant described for mast cells and conceivably relevant, because pathologic processes mediated by TGF-beta are often associated with mast cell accumulation.

Animals↗

PubMed1995

The modulation of granulomatous tissue and tumour angiogenesis by diclofenac in combination with hyaluronan (HYAL EX-0001).

In a novel application, hyaluronan has been utilized as a delivery system for topical and i.v. therapeutics. Clinical trials and case reports show that topical diclofenac delivered in hyaluronan (HYAL CT-1101) is effective against basal-cell carcinoma and actinic keratosis. The effect of this drug formulation on tumour growth and angiogenesis, as well as granulomatous tissue angiogenesis, has been investigated experimentally. The evidence that hyaluronan has a permissive effect on the inhibition of granulomatous tissue angiogenesis by diclofenac (as assessed by the carminel/gelatin vascular casting method) when injected into the lesion or applied topically is reviewed. Topical diclofenac in hyaluronan also induces a regression of the existing neo-vasculature of granulomatous tissue when applied therapeutically. The diclofenac formulated in hyaluronan was also found to be profoundly effective against the development of subcutaneous Colon-26 tumours in syngeneic balb/c mice (T/C ratio after 12 days topical application of 0.174, p < 0.0001). Analysis of the tumour vasculature showed that vascular development was retarded by 12 days. This was shown by the reduction in the tumour density of carmine in the vascular casts, as well as reduced blood-vessel density visualized by rat anti-mouse CD31 immunohistology. Hyaluronan alone had a significant effect on tumour development with a 50% inhibition of tumour growth and only a transient reduction in vascularity. The effects noted when diclofenac is formulated in hyaluronan, and applied topically, could be related to trans-dermal delivery and deposition properties of hyaluronan, and to the binding properties of hyaluronan to areas of pathology with high expression of hyaluronan receptors such as RHAMM, ICAM-1, and CD44.

Animals↗

PubMed1995

Angiogenesis in pre-eclampsia.

OBJECTIVE: To study the angiogenetic activity of decidua basalis from primigravid women with pre-eclampsia. STUDY DESIGN: Fresh fragments of decidua basalis from 10 primigravid women with pre-eclampsia and from 10 healthy, control primigravid women, were grafted onto the chick embryo chorioallantoic membrane (CAM) at the 6th incubation day. Four days later the CAMs were fixed and the angiogenic response of the CAMs was assessed on histologic sections by a planimetric point-count method. RESULTS: Decidua from pre-eclamptic pregnancies induced angiogenesis to a greater extent than that from normotensive pregnancies. CONCLUSIONS: Angiogenesis might be stimulated in pre-eclampsia through endothelia and decidua changes induced by the pathological condition which, in turn, would lead to a greater expression of angiogenic factors also present in normal condition.

Allantois↗

PubMed1990

Carcinoma in situ of the cornea.

Carcinoma in situ of the cornea is part of a pathological entity, which covers all conjunctival and corneal epithelial neoplasiae (CIN). The clinicopathological characteristics of this rare ocular tumor will be demonstrated.

Adult↗

PubMed1992

Platelet-derived growth factor is angiogenic in vivo.

PDGF receptors have recently been found to be expressed in microvascular endothelium in vivo under circumstances of endothelial cell activation and angiogenesis suggesting that PDGF may have a direct effect on endothelial cells. We have tested the angiogenic activity of PDGF-AA and -BB homodimers in the chick chorioallantoic membrane in vivo. PDGF-BB was found to consistently induce an angiogenic response whereas PDGF-AA was less active. Morphological analyses revealed that there was little inflammation associated with this response but an increase in vessel density suggested a direct effect of PDGF on embryonic chorioallantoic endothelial cells. In vitro, PDGF-BB was found to be more potent than PDGF-AA in stimulating the chemotaxis of rat brain capillary endothelial cells. This is consistent with a direct effect of PDGF on endothelial cells. Thus, this novel angiogenic activity of PDGF has implications for several developmental and pathological events in which PDGF, particularly the B-chain, is expressed.

Allantois↗

PubMed1990

Comparison of Dolichos biflorus lectin and other lectin-horseradish peroxidase conjugates in staining of cutaneous blood vessels in the hairless mini-pig.

Angiogenesis is necessary for normal growth, wound healing, and plays a key role in many pathologic processes. A variety of endothelial markers have been used to investigate angiogenesis. Unfortunately, excellent markers for vascular endothelium in human tissues exhibit little or no staining of endothelia in tissues of other animal species, including the pig. We are interested in the hairless Yucatan strain of mini-pig as an animal model for studying cutaneous wound healing because its skin is histologically and functionally very similar to that of man. Hoping to find a specific marker to identify vascular endothelium in the mini-pig, we therefore screened a battery of 11 different lectin-horseradish peroxidase conjugates. Based on specificity and staining intensity, Dolichos biflorus agglutinin (DBA) was chosen from this battery to investigate vascular changes in the healing of cutaneous wounds in the mini-pig. When compared with routine histologic sections stained with hematoxylin and eosin, blood vessels were much easier to identify in sections stained histochemically with DBA. Lectin histochemistry was particularly useful in investigations of early events in angiogenesis during wound healing when newly derived capillary buds and minute blood vessels were obscured in normal histologic sections by an inflammatory cell infiltrate associated with the healing wound. Ultrastructural lectin cytochemistry revealed staining along the luminal surface and the basolateral plasmalemma of endothelial cells. Histochemical staining with DBA promises to provide a useful method for further investigation of angiogenesis and other vascular phenomena in a variety of normal and pathologic processes using the hairless Yucatan strain of mini-pig as the animal model.

Animals↗

PubMed1991

Angiotensin and the regulation of cellular growth. Pathophysiologic implications for cardiovascular and noncardiovascular tissues.

Components of the renin-angiotensin system can be found in the vasculature, although in most cases it is unclear how much, if any, of this renin in the vasculature is locally synthesized. Over recent years, a variety of novel actions of angiotensin II have been delineated which suggest that in appropriate physiologic or pathologic circumstances vascular angiotensin II can play an important role in determining vascular structure. Moreover, angiotensin II may play a role in neoplastic growth of vascular and nonvascular tissues.

Angiotensin II↗

PubMed1990

[Experimental study of an axial vascularized pedicle flap induced in rats].

The authors report an experimental study about induced flaps in rats. The aim of this study is to determine that neoangiogenesis can be formed from surgically introduced pedicle. Two main groups were studied: in the first one the arteriovenous pedicle was be anastomased at its distal end, in the other, an arteriovenous loop was created microsurgically. In both groups we obtained good results and the flaps stayed alive. Neoangiogenesis from the surgically introduced axial pedicle was observed. The prospects in human pathology are interesting to consider, for the surgeon might be liberated from the narrow anatomic limits imposed by vascular territories, by creating a suitable flap anywhere in the body.

Graft Survival↗

PubMed1996

Neoangiogenesis: a putative marker of malignancy in non-small-cell lung cancer (NSCLC) development.

Several studies have documented a relevant prognostic role of microvessel count (MC) in non-small-cell lung carcinomas (NSCLC). However, no evidence has been reported about the involvement of neo-angiogenesis in the development of bronchial cancers. The aim of this study was to analyze microvessel density both in normal and in pathological features of the bronchial tree detected concomitantly with carcinomas. In a group of 34 patients resected for NSCLC, 48 bronchial lesions (hyperplasia, squamous metaplasia, moderate dysplasia and in situ carcinoma) were identified. In addition, 20 samples of normal bronchial epithelium from the same patients were analyzed. A monoclonal antibody was used in order to identify microvessels in the most intense areas of neovascularization from the bronchial specimens. MC was also analyzed in invasive components. An increased number of microvessels was observed from normal to dysplastic epithelium, including in situ carcinoma. Mean MC was significantly lower in normal, hyperplastic and squamous metaplastic epithelium than in dysplastic epithelium and in situ carcinoma. In particular, no differences were observed between normal and hyperplastic/metaplastic components, whereas a statistically significant difference appeared between the latter and dysplastic lesions. Moderate dysplasia and in situ carcinoma showed a number of microvessels in the lamina propria of their mucosa which were not significantly different from the invasive component, whereas hyperplastic/metaplastic lesions presented a much lower number of microvessels than invasive cancer. From these data it appears that normal bronchial epithelium and lesions associated with cancers of the bronchial tree show neovascularization in their stromal component. Hyperplasia and squamous metaplasia, unlike dysplasia and in situ carcinoma, show a low microvessel count, and they cannot represent precursor or incipient changes in the bronchial epithelium before the fully developed in situ stage has also been reached.

Carcinoma in Situ↗

PubMed1991

Microsurgical management of neovascularisation secondary to posterior segment ischaemia.

Structural, metabolic and functional rehabilitation of eyes affected by the haemorrhagic and tractional sequelae of neovascularisation secondary to posterior segment ischaemia is discussed. Microsurgical management must pay due attention not only to the mechanical but also to the underlying cell-biological implications of the surgical pathology. The appropriateness of case selection for surgery rests upon the likelihood of successful technical and functional outcomes and also upon the overall visual status of the patient, issues of particular relevance to diabetes.

Diabetic Retinopathy↗

PubMed1990

Developing testicular microvasculature in the golden hamster, Mesocricetus auratus: a model for angiogenesis under physiological conditions.

The ultrastructure of the developing testicular microvasculature in the testes of immature (3, 5, 8, 10, 12, 16, 20, 25, 30 and 35 days old) golden hamsters was examined and compared to the testicular microvasculature of adult (3 months old) hamsters. In addition, in 16- to 35-day-old hamsters vascular permeability was studied after localization of injected horseradish peroxidase (HRP). Angiogenic processes were present in the testes of all examined immature hamsters and were most conspicuous between 8 and 25 days of age. These processes were absent in the testes of 3-month-old hamsters. On days 3 and 5, few undifferentiated blood vessels with activated endothelium were present in the interstitial spaces. Endothelial cell migration started from these 'mother vessels' and led to invasion of intertubular spaces by vascular sprouts, before vascularization of peritubular spaces occurred (after day 12). Sprouting endothelial cells were identified by the presence of a basal lamina and characterized by abundant cytoplasm and cell organelles. HRP-positive slits were seen in developing vessels, which opened to form the vascular lumen. HRP exited the vascular lumen through unspecialized endothelial contacts and micropinocytotic vesicles. By day 16, the blood-testis barrier prevented HRP from entering the seminiferous tubules beyond the basal compartment. By days 30 and 35 most testicular microvessels and at the age of 3 months all testicular microvessels were of the mature type, with narrow inactive endothelium and specialized cell contacts (including tight junctions). These results demonstrate that the postnatal vascularization of the testis in the golden hamster is a timed complex process. Due to high permeability, vascular sprouts are likely to influence the metabolic situation and thus the maturation processes of the testis. Angiogenesis in the golden hamster testis shares typical morphological features with angiogenic processes in other organs and species under various pathological and physiological conditions. We therefore conclude that the postnatal testis can be viewed as a physiological model of angiogenesis.

Animals↗