Disease relevance of Neovascularization, Pathologic

• Vascular endothelial growth factor (VEGF) is a potent angiogenic factor involved in physiological and pathological angiogenesis, and elevated levels of VEGF are found in peritoneal fluid of patients with endometriosis [1].
• Given the proposed hypothesis of the close linkage between diabetic angiopathy and ROS, those data suggest that ROS-associated diabetic complication may involve ATF3-mediated pathological angiogenesis [2].
• It is unclear, however, how PlGF, which is elevated in proliferative diabetic retinopathy and is a VEGF homolog that binds only to VEGF receptor (VEGFR)-1, promotes pathological angiogenesis [3].
• Thus, VEGF might regulate the function of both retinal endothelial cells and retinal pericytes to induce pathological angiogenesis and vascular remodeling during proliferative diabetic retinopathy and other ischemic retinal diseases [4].
• Administration of recombinant ExTek protein or an ExTek adenovirus inhibited tumor growth and metastasis in rodent tumor models, demonstrating a functional role for Tie2 in pathological angiogenesis in adult tissues [5].

High impact information on Neovascularization, Pathologic

• Akt1 regulates pathological angiogenesis, vascular maturation and permeability in vivo [6].
• VEGF has also been implicated in pathological angiogenesis associated with tumors, intraocular neovascular disorders and other conditions [7].
• Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins [8].
• These data indicate that alphavbeta3 and alphavbeta5 integrins are not essential for vascular development or pathological angiogenesis and highlight the need for further evaluation of the mechanisms of action of alphav-integrin antagonists in anti-angiogenic therapeutics [8].
• These results suggest that PEDF may be of therapeutic use, especially in retinopathies where pathological neovascularization compromises vision and leads to blindness [9].

Chemical compound and disease context of Neovascularization, Pathologic

• The vascular endothelial growth factor (VEGF) receptor fetal liver kinase 1 (flk1; VEGFR-2, KDR) is an endothelial cell-specific receptor tyrosine kinase that mediates physiological and pathological angiogenesis [10].
• To investigate the role of HLF in adult pathological angiogenesis, we generated HLF-knockdown (HLF(kd/kd)) mice by inserting a neomycin gene sandwiched between two loxP sequences into exon 1 of the HLF gene [11].
• CM101, a polysaccharide isolated from the culture medium of Group B streptococcus, a neonatal pathogen, targets pathological angiogenesis and inhibits tumor growth in mice and humans [12].
• In this review, the complex mechanisms of action of the serine proteases in pathological angiogenesis are summarized alongside possible therapeutic applications [13].
• Vascular endothelial growth factor (VEGF)-A is an important angiogenic cytokine in cancer and pathological angiogenesis and has been related to the antiangiogenic activity of dopamine in endothelial cells [14].

Biological context of Neovascularization, Pathologic

• Since ADAM15 does not appear to be required for developmental angiogenesis or for adult homeostasis, it may represent a novel target for the design of inhibitors of pathological neovascularization [15].
• Up-regulation of placental growth factor (PlGF), a member of the vascular endothelial growth factor (VEGF) family, has been found in several conditions associated with pathologic angiogenesis; however, its distinct role in the control of angiogenesis has remained unclear [16].
• Vascular endothelial growth factor (VEGF) is a primary regulator of physiological angiogenesis and is a major mediator of pathological angiogenesis, such as tumor-associated neovascularization [17].
• Together, these findings indicate that PlGF-containing ligands contribute to pathological angiogenesis by prolonging cell survival signals and maintaining vascular networks [3].
• Vascular endothelial growth factor receptor (VEGFR)-2 plays a critical role in vasculogenesis during embryonic development and pathological angiogenesis, but little is known about the molecular mechanisms governing its functions [18].

Anatomical context of Neovascularization, Pathologic

• These results provide novel evidence that Cav-1 and caveolae play an important positive role in the process of pathological angiogenesis in vivo [19].
• In this study, we have demonstrated that ang2 mRNA levels are increased in the retina during development of the deep retinal capillaries by angiogenesis and during pathologic angiogenesis in a model of ischemic retinopathy [20].
• Nitric oxide mediates interleukin-1-induced matrix degradation and basic fibroblast growth factor release in cultured rabbit articular chondrocytes: a possible mechanism of pathological neovascularization in arthritis [21].
• By contrast, systemic administration of cytogenin (100 mg/kg p.o., for 5 consecutive days) significantly suppressed angiogenesis induced by malignant tumor cells (S-180), one of pathological neovascularization, in a mouse dorsal air sac assay system [22].
• CONCLUSIONS: TP is expressed consistently in normal and hyperplastic endometrium, suggesting a role in physiological and pathological angiogenesis [23].

Gene context of Neovascularization, Pathologic

• Here we show that Akt1 is the predominant isoform in vascular cells and describe the unexpected consequences of Akt1 knockout on vascular integrity and pathological angiogenesis [6].
• Involvement of Flt-1 tyrosine kinase (vascular endothelial growth factor receptor-1) in pathological angiogenesis [24].
• Few therapeutic options currently exist for HGF/SF-induced pathological angiogenesis, and the vast knowledge on COX-2 inhibitors can be harnessed to design a newer therapeutic approach [25].
• CLIC4 was expressed at high levels in resting vessels, whereas expression was modulated during pathological angiogenesis such as in tumor vessels [26].
• Recent studies have shown that the angiopoietin-Tie2 system is a major regulator of vascular integrity and is involved in pathologic angiogenesis [27].

Analytical, diagnostic and therapeutic context of Neovascularization, Pathologic

• Overexpression of TIMP-3 by ECs may be considered a gene therapy strategy for the treatment of pathological angiogenesis such as cancer and diabetic retinopathy [28].

References