Negative regulation of angiogenesis by zinc-finger transcription factor TCF8
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The concept of angiogenesis and consecutive stages of the neovascularization processes under physiological and pathological conditions have been described. Angiogenesis is regulated by the different mechanisms which are in dynamic balance. The regulating components of these processes are the stimulating and inhibiting factors, the mediators of these reactions under influence of the host cell-tumor cell interaction. The role of angiogenesis in cancer development is connected with obtaining the angiogenic phenotype by tumor when the transformation from prevascular to vascular phase of neoplasm goes on. The further tumor growth and metastasis processes depend on neovascularization. Actual research trends in the field of angiogenesis have been presented in this paper. We need to know such markers of angiogenesis would be the most useful for doing research work and monitoring neoplasm diseases in clinics. Antiangiogenic management seems to be a new promising therapeutic concept in oncology.
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OBJECTIVE To explore the relationship between hypoxia-inducible foctor-1α (HIF-1α) and neovascularization in early atherosclerosis plaques by establishing rabbit carotid atherosclerosis models, and to observe the value of contrast-enhanced ultrasound in the detection of neovascularization. METHODS We provided high-fat diet combined with the implantation of silicone rubber ring to establish carotid atherosclerosis in rat models. On the 14th and 28th days, we detected neovascularization in the carotid atherosclerotic plaques by contrast-enhanced ultrasound, obtained the peak intensity (PI) of the contrast agent in the plaques by time-intensity curve (TIC) and analyzed the difference. We also tested the level of HIF-1α, vascular endothelial growth factor (VEGF), cluster of differentiation 31 (CD31), α-actin, and RAM-11 by immunohistochemical method in each group, analyzed their correlation, and the correlation between PI and CD31 expression. RESULTS On the 14th day, contrast-enhanced ultrasound showed the neovascularization in the carotid atherosclerotic plaques. On the 14th and 28th days, the intensity of contrast-enhanced ultrasound showed significant difference, the mean optical density of HIF-1α, VEGF, CD31, RAM-11, and α-actin within the carotid atherosclerotic plaques also showed statistical difference. The expressions between HIF-1α and VEGF, HIF-1α and CD31, HIF-1α and RAM-11, HIF-1α and α-actin, as well as PI and CD31 showed highly positive correlations. CONCLUSION During the process of atherosclerosis evolution, neovascularization in the atherosclerotic plaques has come into being in the early period, and HIF-1α in early atherosclerosis can promote the formation of neovascularization. Contrast-enhanced ultrasound can detect the dynamic changes of neovascularization within early atherosclerotic plaques.
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The formation of new blood vessels from existing blood vessels has been referred to as angiogenesis to distinguish the process from de novo embryonic vessel formation or vasculogenesis (1). This chapter will describe an in vivo assay to measure angiogenesis. There are several important reasons to study and measure angiogenesis in vascular disease. First, it is necessary to try to understand proliferative angiogenesis as it occurs in tumors and in diabetic complications and devise strategies to inhibit it. Second, there is intense interest in improving angiogenesis after ischemia or in chronic wounds (2). Third, many potential modulators of angiogenesis need to be evaluated to determine their effects on blood vessel development.
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