Vascular endothelial growth factor A

About: Vascular endothelial growth factor A is a research topic. Over the lifetime, 15203 publications have been published within this topic receiving 1271498 citations. The topic is also known as: vascular endothelial growth factor A & vascular endothelial growth factor A165.

Role of host angiotensin II type 1 receptor in tumor angiogenesis and growth.

Abstract: Although the renin angiotensin system (RAS) is a major regulator of vascular homeostasis, the role of the RAS in tumor angiogenesis is little understood. Here we show that host angiotensin II (ATII) type 1 (AT1) receptor plays an important role in angiogenesis and growth of tumor cells engrafted in mice. Subcutaneous B16-F1 melanoma-induced angiogenesis as assessed by tissue capillary density and microangiography was prominent in WT mice but was reduced in AT1a receptor–deficient (AT1a–/–) mice. Consequently, tumor growth rate was significantly slower, and the mouse survival rate was greater, in AT1a–/– mice than in WT mice. Tumor growth was also reduced in WT mice treated with TCV-116, a selective blocker of AT1 receptor. Because the β-galactosidase gene was inserted into the AT1a gene locus in AT1a–/– mice, the site of β-galactosidase expression represents the AT1a receptor expression in these mutant mice. In tumor-implanted AT1a–/– mice, the major site of the β-galactosidase expression was macrophages in tissues surrounding tumors. Moreover, the number of infiltrated macrophages was significantly lower in AT1a–/– mice than in WT mice, and double-immunofluorescence staining revealed that these macrophages expressed VEGF protein intensively. Therefore, the host ATII-AT1 receptor pathway supports tumor-associated macrophage infiltration, which results in enhanced tissue VEGF protein levels. The host ATII-AT1 receptor pathway thereby plays important roles in tumor-related angiogenesis and growth in vivo.

Expression of the Vascular Endothelial Growth Factor (VEGF) Receptor Gene, KDR, in Hematopoietic Cells and Inhibitory Effect of VEGF on Apoptotic Cell Death Caused by Ionizing Radiation

Abstract: Vascular endothelial growth factor (VEGF) has been identified as a peptide growth factor specific for vascular endothelial cells. In this study, we demonstrated the expression of the KDR gene transcript, which encodes a cell surface receptor for VEGF, in normal human hematopoietic stem cells, megakaryocytes, and platelets as well as in human leukemia cell lines, HEL and CMK86. Moreover, we showed the expression of VEGF gene transcript in these normal fresh cells and cell lines. To elucidate biological functions of VEGF on hematopoiesis, we determined whether this growth factor has mitogenic activity to hematopoietic cells or the ability to suppress apoptotic cell death. The liquid culture and colony-formation assay revealed that VEGF suppressed apoptotic cell death of both CMK86 cells and normal hematopoietic stem cells caused by gamma-ray irradiation, although mitogenic activity of VEGF was not detected. The ability of VEGF to suppress apoptotic cell death was independent of the change of cell cycle distribution. These data suggest that VEGF may play an important role in survival or maintenance of hematopoietic stem cells due to the prevention of apoptotic cell death caused by some stresses such as ionizing radiation and that VEGF may give leukemia cells some abilities of resistance against radiotherapy in an autocrine or paracrine manner.

Angiogenesis : a dynamic balance of stimulators and inhibitors

Abstract: Angiogenesis, the formation of new blood vessels from a pre-existing vasculature, is tightly regulated in normal adults. Under physiological circumstances, angiogenesis occurs in only a few instances; e.g., the female reproductive system in response to ovulation or gestation, the normal hair cycle, etc. In these examples, growth of new capillaries is tightly controlled by an interplay of growth regulatory proteins which act either to stimulate or to inhibit blood vessel growth. Normally, the balance between these forces is tipped in favor of inhibition and consequently capillary growth is restrained. Under certain pathological circumstances, however, local inhibitory controls are unable to restrain the increased activity of angiogenic inducers. Thus, in wound healing, inflammation and tumors, to name just a few examples, angiogenesis is integral to the pathology, engendering the hope that these pathological entities could be regulated by pharmacological and/or genetic suppression (or enhancement) of blood vessel growth. This hope, in turn, has fostered interest in the molecular mechanisms that regulate angiogenesis. In this chapter, we have reviewed the current literature regarding some angiogenic stimulators and inhibitors, emphasizing vascular permeability factor (VPF, also known as vascular endothelial growth factor or VEGF), as a major angiogenic inducer, and thrombospondin (TSP) as the best known example of a natural inhibitor of vessel growth.