Anemia ; metabolism ; physiopathology ; Animals ; Cell Hypoxia ; Genetic Therapy ; Humans ; Hypoxia-Inducible Factor 1 ; genetics ; metabolism ; physiology ; Neovascularization, Pathologic ; metabolism ; pathology ; Neovascularization, Physiologic ; Osteogenesis ; RNA, Messenger ; metabolism

Adult ; Aged ; Angiopoietin-2 ; physiology ; Female ; Glioma ; blood ; physiopathology ; Humans ; Hypoxia ; blood ; metabolism ; Male ; Middle Aged ; Neovascularization, Pathologic ; physiopathology

Dysregulation of the Wnt pathway has been extensively studied in multiple diseases, including some angiogenic disorders. Wnt signaling activation is a major stimulator in pathological angiogenesis and thus, Wnt antagonists are believed to have therapeutic potential for neovascular disorders. Actually, some Wnt antagonists have been identified directly from the anti-angiogenic factor family. This review summarizes the recent progress toward understanding of the roles of Wnt pathway antagonists in angiogenic regulation and their mechanism of action, and exploring their therapeutic potential.
Adaptor Proteins, Signal Transducing ; metabolism ; Animals ; Humans ; Neovascularization, Pathologic ; physiopathology ; Repressor Proteins ; metabolism ; Signal Transduction ; physiology ; Wnt Proteins ; antagonists & inhibitors

Cell Movement ; drug effects ; Chemokine CXCL12 ; genetics ; metabolism ; pharmacology ; physiology ; Humans ; Neoplasm Invasiveness ; physiopathology ; Neoplasm Metastasis ; physiopathology ; Neoplasms ; metabolism ; Neovascularization, Pathologic ; physiopathology

OBJECTIVETo investigate the effects of Shexiang Baoxin Pill (SBP) in intervening atherosclerosis and myocardial infarction (AS-MI) in experimental animals, and inspect its influences on angiogenesis.

METHODSTwenty male New-Zealand rabbits were made into AS-MI model, and randomly divided into 2 groups equally. Group A was fed with high-fat diet for control; Group B was fed with high-fat diet but intervened with SBP. The cardiac function and the positive area of plaque were determined. The CD34 positive response intensity at infarcted marginal zone and aorta vessel wall, and the capillary density of myocardium were measured by immunohistochemical staining. In addition, the protein expressions of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2) were detected by Western blot.

RESULTSCompared to Group A, the cardiac function was obviously improved (P<0.05) and the plaque positive area (%) was significantly decreased in Group B (45.82 +/- 3.68 vs 82.56 +/- 4.97, P<0.01). The CD34 positive response intensity and the capillary density as well as VEGF and VEGFR-2 expressions in infarcted marginal zone in Group A were higher than those in Group B (P<0.01); but these parameters at aorta vessel walls were lower in Group A than in Group B (P<0.01).

CONCLUSIONSBP could advance the angiogenesis in the marginal zone of infarction, improve heart function, and embarrass angiogenesis in atherosclerotic plaque.

Animals ; Atherosclerosis ; physiopathology ; Drugs, Chinese Herbal ; pharmacology ; Male ; Myocardial Ischemia ; physiopathology ; Neovascularization, Pathologic ; physiopathology ; prevention & control ; Neovascularization, Physiologic ; drug effects ; Plaque, Atherosclerotic ; pathology ; physiopathology ; Rabbits ; Random Allocation ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

Neovascularization of the adventitial vasa vasorum with extension into the intima of atherosclerotic lesions is frequently observed, but its pathophysiological significance is still subject to debate. Recently, leptin, the product of the Ob gene, was identified. Leptin, via activation of the endothelial receptor (Ob-R), generates a growth signal involving a tyrosine kinase-dependent intracellular pathway and promotes angiogenic processes. We hypothesized that a high concentration of leptin within vasa vasorum and plaque itself, may influence inflammatory and vascular neovascularization coupling with functional upregulation of the vascular endothelial growth factor (VEGF). Microscopic computerized tomography was utilized for the spatial distribution of vasa vasorum and intimal neovascularization from atherosclerotic human coronary arteries. Atherosclerotic coronary arteries showed a dense plexus of microvessels in the adventitia and plaque itself. Microscopic analysis from human atherosclerotic aortas revealed an increase in the intimal thickness with neovascularization. The immunoreactivity for Ob-R, VEGF and matrix metalloproteinase (MMP) increased in atherosclerotic plaque, predominantly in the endothelial lining of the intimal neovessel and macrophages/foam cells. Our observation of a prominent colocalization between Ob-R, VEGF and MMP supports this hypothesis and these factors participate in the neovascularization of atherosclerotic lesions. The present study is the first report on vascular tissue and it opens a promising perspective concerning future investigations of leptin-dependent modulation of atherogenesis and vascular neovascularization under pathophysiolgical conditions.
Adult ; Arteriosclerosis/physiopathology ; Arteriosclerosis/pathology ; Arteriosclerosis/metabolism* ; Blood Vessels/pathology ; Blood Vessels/metabolism ; Carrier Proteins/physiology ; Carrier Proteins/metabolism* ; Human ; Middle Age ; Neovascularization, Pathologic/physiopathology

OBJECTIVETo reseach the correlations between cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) expressions and angiogenesis in pharyngeal tissue of patients with obstructive sleep apnea hypopnea syndrome (OSAHS).

METHODSBiopsies were obtained by uvulopalatopharyngoplasty from 40 patients with mild to severe OSAHS. Control specimens of palatopharyngeal and palatoglossal arch mucosa were retreved from 6 patients with chronic tonsillitis and proved have no related disorders. HE was used to observe the changes of pharyngeal tissue, immunohistochemical staining with antibodies against COX-2, VEGF, microvessel density (MVD) (marked with CD34).

RESULTSCOX-2 and VEGF mainly expressed at pavement-epithelium and glandular epithelium of pharyngeal tissue, and stronger COX-2 and VEGF expression was found in midrange and severe OSAHS than mild and control group (P < 0.01), so as MVD. COX-2 expression was correlated positively with VEGF expression, and had significant correlation with MVD. VEGF expression had the same correlation with MVD. These three targets had considerable relation with apnea hypopnea index (AHI) and lowest O2 saturation at night.

CONCLUSIONThere was angiogenesis which had important relationship with hypoxia degree in patients of OSAHS, and COX-2 and VEGF play a crucial role in its development.

Adult ; Cyclooxygenase 2 ; genetics ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Neovascularization, Pathologic ; Pharynx ; blood supply ; metabolism ; Sleep Apnea, Obstructive ; metabolism ; physiopathology ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

Tumor angiogenesis was simulated using a two-dimensional computational model. The equation that governed angiogenesis comprised a tumor angiogenesis factor (TAF) conservation equation in time and space, which was solved numerically using the Galerkin finite element method. The time derivative in the equation was approximated by a forward Euler scheme. A stochastic process model was used to simulate vessel formation and vessel elongation towards a paracrine site, i.e., tumor-secreted basic fibroblast growth factor (bFGF). In this study, we assumed a two-dimensional model that represented a thin (1.0mm) slice of the tumor. The growth of the tumor over time was modeled according to the dynamic value of bFGF secreted within the tumor. The data used for the model were based on a previously reported model of a brain tumor in which four distinct stages (multicellular spherical, first detectable lesion, diagnosis, and death of the virtual patient) were modeled. In our study, computation was not continued beyond the 'diagnosis' time point to avoid the computational complexity of analyzing numerous vascular branches. The numerical solutions revealed that no bFGF remained within the region in which vessels developed, owing to the uptake of bFGF by endothelial cells. Consequently, a sharp declining gradient of bFGF existed near the surface of the tumor. The vascular architecture developed numerous branches close to the tumor surface (the brush-border effect). Asymmetrical tumor growth was associated with a greater degree of branching at the tumor surface.
Computer Simulation ; Fibroblast Growth Factor 2/metabolism ; Humans ; *Models, Biological ; Neoplasms/*blood supply/metabolism ; Neovascularization, Pathologic/*physiopathology ; Research Support, Non-U.S. Gov't

OBJECTIVETo investigate the effect of small interference RNA (siRNA) targeting nuclear factor-kappaB (NF-kappaB) on endometriosis.

METHODThe eutopic endometrium of women with endometriosis were transplanted into the nonvascular region of 8-day-old chicken embryo chorioallantocic membrane (CAM), and the effects of NF-kappaB p65 siRNA on the vascularization and endometriotic lesion formation were tested with proper controls.

RESULTSTransplantation of the endometrium onto the CAM resulted in a strong angiogenic response in the chicken tissue. The angiogenesis was significantly reduced and endometriotic lesion formation significantly suppressed with siRNA targeting NF-kappaB in comparison with the control group.

CONCLUSIONSThe NF-kappaB pathway is involved in the development of endometriotic lesions in vitro, and NF-kappaB gene silencing reduces endometriotic angiogenesis and promotes cell apoptosis in the endometriotic lesions, suggesting that NF-kappaB might be a good target for endometriosis treatment.

Animals ; Chick Embryo ; Chorioallantoic Membrane ; blood supply ; metabolism ; Endometriosis ; genetics ; physiopathology ; Female ; Humans ; NF-kappa B ; deficiency ; genetics ; Neovascularization, Pathologic ; genetics ; RNA Interference ; RNA, Small Interfering ; genetics

OBJECTIVETo investigate the reactivity of colon cancer cell line SW480 and CD133(+) SW480 subsets to hypoxia in vitro and the changes in the expressions of anti-apoptosis and angiogenesis genes.

METHODSSW480 cells was subjected to CoCl(2) exposure at varying concentrations and for different time lengths to induce hypoxia, and the protein expression of hypoxia induced factor 1α (HIF-1α) was detected by Western blotting. The CD133(+) SW480 cells were sorted by magnetic activated cell sorting (MACS) and their proportion was assayed by flow cytometry (FCM). The CD133(+) SW480 subsets were exposed to CoCl(2) at the optimal concentration with exposure time selected in terms of HIF-1α level, and their tumor stem cell sphere formation ability was evaluated. Real-time PCR was used to compare the mRNA expression levels of the surface markers of colon cancer stem cells (CD133 and PROM1), survivin, and vascular endothelial growth factor (VEGF).

RESULTSExposure to 200 µmol/L CoCl(2) for 8 h resulted in the highest HIF-1α expression in SW480 cells, but the same exposure failed to induce HIF-1α expression in CD133(+) SW480 subsets. The CD133(+) SW480 subsets, after CoCl(2)-induced hypoxia, showed significantly enhanced ability of cell sphere formation. Hypoxia of SW480 cells caused significant increases in CD133, survivin and VEGF mRNA levels by 1.607∓0.103, 2.745∓0.370 and 3.798∓0.091 folds, respectively (P<0.05).

CONCLUSIONCoCl(2) can simulate hypoxia in colon cancer cells in vitro to induce stable HIF-1α expression, which is concentration- and time-dependent. The hypoxia-stimulated tumor stem sells show an enhanced sphere formation and anti-apoptotic and anti-angiogenic abilities.

Apoptosis ; physiology ; Cell Hypoxia ; Cell Line, Tumor ; Colonic Neoplasms ; pathology ; Computer Simulation ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Neoplastic Stem Cells ; pathology ; Neovascularization, Pathologic ; physiopathology