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PubMed1986

[Diabetic choroidopathy--a retrospective fluorescein angiography study. Preliminary report].

Both histologic studies and findings with Indocyanin green angiography furnish clear indications of the existence of diabetic choroidopathy. Out of 19,387 fluorescein angiograms made over the last 15 years at the First Ophthalmological Clinic of Vienna University, 902 were selected in which the choroidal vascular system is at least partially visible due to melanin hypopigmentation. The pathologic changes in the choroid observed in these angiograms can be allocated in two basic types of pathologic fluorescence: on the one hand hyperfluorescent lesions such as drusen in Bruch's membrane in suprisingly young diabetics, extremely hyperfluorescent lobules of the choriocapillaris, choroidal aneurysms, and neovascularizations; on the other hand, hypofluorescent lesions or structures were observed, such as delayed filling of the choriocapillaris and, in the late phase of angiography, varicose and tortuous choroidal vessels, drained and appearing dark in contrast to the diffuse background fluorescence.

Aneurysm↗
PubMed2006

Biology of vascular endothelial growth factors.

Angiogenesis is the process by which new blood vessels are formed from existing vessels. The vascular endothelial growth factors (VEGFs) are considered as key molecules in the process of angiogenesis. The VEGF family currently includes VEGF-A, -B, -C, -D, -E, -F and placenta growth factor (PlGF), that bind in a distinct pattern to three structurally related receptor tyrosine kinases, denoted VEGF receptor-1, -2, and -3. VEGF-C and VEGF-D also play a crucial role in the process of lymphangiogenesis. Here, we review the biology of VEGFs and evaluate their role in pathological angiogenesis and lymphangiogenesis.

Arthritis, Rheumatoid↗
PubMed1997

Factors controlling ocular angiogenesis.

PURPOSE: To provide an overview of the cellular and molecular factors involved in ocular angiogenesis. METHODS: A literature search and review encompassing a broad range of medical and basic science disciplines was undertaken to survey contemporary insights into the mechanisms of angiogenic stimulation and inhibition. RESULTS: Ocular angiogenesis is a complex pathophysiologic process. Factors have been isolated that play key roles in the regulation of angiogenesis. The influence of stimulating growth factors is counterbalanced by a number of antiproliferative agents. The net result of these opposing factors on the vascular endothelial cell determines the outcome of angiogenesis homeostasis. Both endogenous and synthetic molecules can regulate ocular angiogenesis. CONCLUSIONS: The isolation and synthesis of molecular regulators of angiogenesis has enhanced our understanding of this process. Clinical trials are underway to determine the efficacy of these agents in controlling pathologic angiogenesis, including that in ocular disease.

Endothelium, Vascular↗
PubMed1999

Inhibition of tumor growth and metastasis by targeting tumor-associated angiogenesis with antagonists to the receptors of vascular endothelial growth factor.

Angiogenesis, the formation of new blood vessels, is essential for both tumor growth and metastasis. Recent advances in our understanding of the molecular mechanisms underlying the angiogenesis process and its regulation have led to the discovery of a variety of pharmaceutical agents with anti-angiogenic activity. The potential application of these angiogenesis inhibitors is currently under intense clinical and pre-clinical investigation. Compelling evidence suggests that vascular endothelial growth factor (VEGF) and its receptors play critical roles in tumor-associated angiogenesis, and that they represent good targets for therapeutic intervention. This has been demonstrated in a variety of animal tumor models in which disabling the function of VEGF and its receptors was shown to inhibit both tumor growth and metastasis. We have produced a panel of antibodies directed against the VEGF receptor 2, KDR/F1k-1. These antibodies potently block VEGF/KDR/F1k-1 interaction, and inhibit VEGF-stimulated activation of the receptor and proliferation of human endothelial cells. Further, the antibodies significantly inhibited tumor-associated angiogenesis in several animal models. Antagonists of VEGF and/or its receptors may offer higher specificity towards tumors with reduced side effects, and may be less likely to elicit drug resistance compared to conventional therapy. Anti-angiogenesis therapy represents a novel strategy for the treatment of cancer and other human disorders where pathological angiogenesis is involved.

Angiogenesis Inhibitors↗
PubMedDate not supplied

[Hyperglycemia and angiogenesis].

Vascular complications of chronic hyperglycemia cause most of diabetes-associated morbidity and mortality. Main targets of chronic hyperglycemia are vascular endothelial cells. Ischemia is the late consequence of vascular damage in patients with diabetes and triggers an angiogenic response. In patients with diabetes, the angiogenic response to chronic ischemia can be excessive in some of the target organs and insufficient in others, in the same individual. The direct effects of hyperglycemia on the expression level of vascular growth factors have been variably appreciated and depend on the studied organ and model. Beyond the described effects of hyperglycemia on the expression level of vascular growth factors, direct and indirect effects of hyperglycemia on endothelial cell proliferation, extra-cellular matrix and metalloproteases might be involved in the pathology of angiogenesis in diabetes.

Cell Division↗
PubMed2006

[Research on physiological and pathophysiological functions of calreticulin].

Calreticulin (CRT) is an essential Ca2+-binding /storage chaperone resident protein of endoplasmic reticulum or sarcoplasmic reticulum found across a diverse range of species. The protein is involved in the regulation of intracellular Ca2+ homeostasis and endoplasmic reticulum Ca2+ storage capacity, and is also an important molecular chaperone involved in "quality control" within secretory pathways. Playing an important role in apoptosis, cell adhesion, gene expression and autoimmunity, calreticulin is involved in the genesis, development and prognosis of many diseases. Now we summarized the physiological function of CRT and its expression changes during myocardial hypertrophy, heart failure, angiogenesis, stresses and many other pathological conditions.

Animals↗
PubMed2004

Vasculogenesis and angiogenesis.

Two distinct mechanisms, vasculogenesis and angiogenesis implement the formation of the vascular network in the embryo. Vasculogenesis gives rise to the heart and the first primitive vascular plexus inside the embryo and in its surrounding membranes, as the yolk sac circulation. Angiogenesis is responsible for the remodeling and expansion of this network. While vasculogenesis refers to in situ differentiation and growth of blood vessels from mesodermal derived hemangioblasts, angiogenesis comprises two different mechanisms: endothelial sprouting and intussusceptive microvascular growth (IMG). The sprouting process is based on endothelial cell migration, proliferation and tube formation. IMG divides existing vessel lumens by formation and insertion of tissue folds and columns of interstitial tissue into the vessel lumen. The latter are termed interstitial or intervascular tissue structures (ITSs) and tissue pillars or posts. Intussusception also includes the establishment of new vessels by in situ loop formation in the wall of large veins. The molecular regulation of these distinct mechanisms is discussed in respect to the most important positive regulators, VEGF and its receptors flk-1 (KDR) and flt-1, the Angiopoietin/tie system and the ephrin-B/EpH-B system. The cellular mechanisms and the molecular regulation of angiogenesis in the pathological state are summarized and the differences of physiological and pathological angiogenesis elaborated.

Angiopoietin-1↗
PubMed1998

Internal division of capillaries in rat skeletal muscle in response to chronic vasodilator treatment with alpha1-antagonist prazosin.

Chronic vasodilatation represents a stimulus for capillary growth associated with increased luminal shear stress. We have examined the ultrastructure of more than 2000 capillaries to establish whether the sequence of angiogenesis in response to this stimulus is similar to that described during development and under pathological circumstances. Administration of the alpha1-blocker prazosin to rats for 2 weeks led to a greater capillary length density in extensor hallucis proprius muscles without any change in capillary tortuosity: Jv(c,f)=262+/-54 compared with 350+/-17 mm-2, control compared with prazosin (P<0.002). There were obvious signs of endothelial cell (EC) activation after prazosin treatment, including an increased proportion of capillaries with rough endoplasmic reticulum, large cytoplasmic vacuoles, thickened endothelium and an irregular luminal surface. Capillaries from control muscles had a maximum of three ECs in cross section, whereas four ECs were noted in 0.8+0.5% of capillaries after 1 week (n.s.) and 2.5+/-0.9% after 2 weeks (P<0.01) of treatment. This could be due to elongation and/or migration of ECs, as cell proliferation has not been described at these time points. There was also an increase in the proportion of capillaries having a narrow, slit-like lumen (1.7+/-0. 8% of controls; 7.1+/-1.9% at 1 week; 8.8+/-2.5% at 2 weeks; P<0.02), some of which were smaller in size (less than 2 microm diameter) than in controls (3-5 microm) and/or "seamless", i.e. lacking EC junctions. These may represent newly formed vessels. Focal discontinuity of the basement membrane and abluminal EC processes were rarely seen, and capillary growth by abluminal sprouting appeared to be very infrequent (less than 0.001% of profiles). Of more importance was growth starting from the luminal side. Significantly more thin cytoplasmic processes were observed protruding into the lumen of capillaries after 1 week (47.5+/-6.2%, P<0.001) and 2 weeks of prazosin (34.2+/-5.5%, P<0.05) than in control vessels (16.7+/-3.9%). Some of these traversed the entire lumen and connected with endothelium of the opposite side, probably involving membrane fusion, resulting in the appearance of a double lumen. Individual capillaries with a complete double lumen were observed after 2 weeks' prazosin but comparatively rarely, in only four out of six muscles. These findings indicate a pattern of luminal growth which is completely different from intussusceptive growth previously described during development, and from the abluminal capillary sprouting seen under pathological circumstances.

Adrenergic alpha-Antagonists↗
PubMed1999

Selective targeting and photocoagulation of ocular angiogenesis mediated by a phage-derived human antibody fragment.

Molecules that selectively target and occlude new blood vessels would be useful for diagnosis and treatment of pathologies associated with angiogenesis. We show that a phage-derived human antibody fragment (L19) with high affinity for the ED-B domain of fibronectin, a marker of angiogenesis, selectively localizes to newly formed blood vessels in a rabbit model of ocular angiogenesis. The L19 antibody, chemically coupled to a photosensitizer and irradiated with red light, mediates complete and selective occlusion of ocular neovasculature and promotes apoptosis of the corresponding endothelial cells. These results demonstrate that new ocular blood vessels can be distinguished immunochemically from preexisting ones and suggest that the targeted delivery of photosensitizers may be effective in treating angiogenesis-related pathologies.

Animals↗
PubMed1987

Laminin-like immunoreactivity in induced new vessels in kitten and mouse eyes.

Laminin is a basement membrane glycoprotein, widely distributed in body tissues. It has been found on capillary basement membranes in both developing and adult retinal vessels. Oxygen-induced retinopathy was produced in kittens and mice by exposing them to a high oxygen environment during the newborn period. When the animals developed a proliferative retinopathy after a period of survival in room air, they were sacrificed and the eyes enucleated and embedded in paraffin wax. Cross-sections were cut and de-waxed. After preliminary digestion with pepsin, we used a fluorescein isothiocyanate (FITC)-labelled double antibody technique to identify laminin-like immunoreactivity (LLIR). LLIR was found on both intravitreal and intraretinal new vessels in the kitten and mouse, indicating that it is probably secreted by endothelial cells during the formation of pathological new vessels.

Animals↗
PubMed2003

Value of power Doppler imaging and the hypoechoic halo in the sonographic detection of foreign bodies: correlation with histopathologic findings.

OBJECTIVE: To present the power Doppler findings and evaluate the hypoechoic rim in increasing the conspicuity of foreign bodies detected on sonography and to correlate the sonographic and histopathologic findings. METHODS: Between 1998 and 2001, all sonographic examinations for evaluation of possible foreign bodies were reviewed retrospectively. Patients who had surgical exploration and pathologic evaluation were included in the study. Gray scale and power Doppler examinations were performed with high-frequency linear array transducers. Histologic evaluation was then correlated with the sonographic findings. RESULTS: Twenty-five patients were referred for evaluation of possible foreign bodies. Twelve patients underwent surgery and had pathologic correlation. Sonography had sensitivity of 92% for the overall detection of foreign bodies. There were 2 false-positive findings in which discrete foreign bodies were not seen at gross inspection, but inflammation and scar tissue were present at histologic examination. Pathologic findings were thought to represent chronic foreign body reactions. Hypervascularity immediately surrounding the foreign bodies was shown on power Doppler imaging in all cases, correlating with granulation tissue and neovascularity on pathologic examinations. The hypoechoic halo was shown in all but 2 cases and correlated with fibrinous exudate, granulation tissue, and collagenous capsule formation. CONCLUSIONS: Sonography is an effective and sensitive tool for the detection of soft tissue foreign bodies. The use of power Doppler imaging may aid in detection of possible foreign bodies by increasing the conspicuity of both the hypoechoic halo and the foreign body itself.

Adolescent↗
PubMed2006

Experience of 100 surgical cases of encapsulating peritoneal sclerosis: investigation of recurrent cases after surgery.

Since 1993, we have performed enterolysis for encapsulating peritoneal sclerosis (EPS) in 86 patients. Five patients died after surgery, but the remaining 81 patients achieved symptomatic improvement. However, some of the surviving patients developed symptoms of intestinal obstruction after several months, and EPS recurrence remains our greatest challenge. In the present study, we identified factors related to recurrence by clinically comparing 47 recurrent and nonrecurrent patients that we were able to follow for more than 2 years after surgery. In the 47 patients we followed, 11 (23.4%) experienced recurrence, and 10 of those patients underwent a second surgery. Four patients needed a third surgery. The mean time to recurrence was 15.2 months, and all patients with recurrence, except one, experienced their recurrence within 20 months. We observed no differences between the recurrent and nonrecurrent patients in follow-up period, age, history of peritoneal dialysis, use or nonuse of steroids after surgery, thickness of the submesothelial compact zone, or inflammatory cell infiltration. However, the number of microvessels was significantly higher in the recurrent patients. Our surgical experience with EPS shows recurrence in approximately 23% of patients. The results of the present study suggest that peritoneal microvascular hyperplasia is a factor involved in recurrence, and that patients with recurrence may have an irreversible pathologic condition and may experience repeated recurrences.

Adolescent↗
PubMed1987

Retinopathy of prematurity. Pathologic correlation of clinical stages.

This article details the pathologic features of recently described clinical stages of vitreoretinopathy associated with premature birth in humans, beginning with a review of retinal angiogenesis in humans and then of the five stages of retinopathy of prematurity, with a description of paramount clinical feature in each stage and then corresponding pathologic changes. The article concludes with a consideration of arrested and reactivated retinopathy.

Humans↗
PubMed1985

On the pathology of the ciliary sulcus.

The so-called ciliary sulcus of the posterior chamber of the eye is the place of fixation for some of the posterior chamber lenses. It is only recently that this borderline between the iris root and the ciliary processes gained more interest among clinical ophthalmologists. Little is known on tissue reactions in ocular diseases at this very location. Possible reactions are presented based on the material of the Department of Ocular Pathology of the University Eye Hospital München. The main result of this study is the finding of marked fibrovascular proliferative reactions in inflammatory diseases, and vascular proliferations in diabetic and postthrombotic neovascular glaucoma. It is suggested that such proliferations might be the source of intraocular bleeding after posterior chamber lens implantation.

Adolescent↗
PubMed1985

Fibrin degradation and angiogenesis: quantitative analysis of the angiogenic response in the chick chorioallantoic membrane.

Fibrin deposition and removal is a feature common to major pathological processes such as wound healing, chronic inflammation and tumour invasion: processes involving the ingrowth of new blood vessels. Low molecular weight fibrin degradation products (MW less than 50,000) are now shown to induce angiogenesis in the chick chorioallantoic membrane (CAM). This effect has also been shown by new quantitative assays to be associated with stimulation of both DNA and protein synthesis. Autoradiography indicates that all cell types in the CAM are stimulated to divide, and it is proposed that fibrin degradation products are a pathological growth factor.

Allantois↗
PubMed1992

Angiogenesis in the female reproductive system.

In adult tissues, capillary growth (angiogenesis) occurs normally during tissue repair, such as in healing of wounds and fractures. Rampant capillary growth is associated with various pathological conditions, including tumor growth, retinopathies, hemangiomas, fibroses and rheumatoid arthritis. The female reproductive organs (i.e., ovary, uterus, and placenta) exhibit dynamic, periodic growth and regression accompanied by equally dramatic changes in rates of blood flow. It is not surprising, therefore, that they are some of the few adult tissues in which angiogenesis occurs as a normal process. Thus, the female reproductive system provides a unique model for studying regulation of angiogenesis during growth and differentiation of normal adult tissues. Ovarian, uterine, and placental tissues recently have been shown to contain and produce angiogenic and anti-angiogenic factors. This review discusses the current state of knowledge regarding angiogenic processes and their regulation in female reproductive tissues. In addition, implications of this research for regulation of fertility as well as for control of angiogenesis in other normal and pathological processes are discussed.

Animals↗