Researchers at the University of Massachusetts Medical School and colleagues have discovered a critical step for blood vessel growth in zebrafish embryos, providing new insight into how vascular systems develop and offering a potential therapeutic target for preventing tumor growth, which depends on vascularization. The researchers have identified a novel microRNA-mediated genetic pathway responsible for new blood vessel growth (angiogenesis) in zebrafish embryos. The work provides new insights into how vascular systems use the forces of existing blood flow to initiate the growth of new vessels. Focusing on the development of the fifth and sixth aortic arches in the zebrafish, senior author Dr. Nathan Lawson described how the forces exerted by blood flow on endothelial cells are a critical component for expressing a microRNA that triggers new vessel development. In the early stages of development, when blood flow is present in the aortic vessels, but the vascular linkages between the two arches have yet to be established, the stimulus provided by active blood flow leads to expression of an endothelial-cell specific microRNA (mir-126). In turn, this microRNA turns on vascular endothelial growth factor (VEGF), a chemical signal produced by surrounding cells that normally stimulates angiogenesis. Thus, blood flow allows the endothelial cells to respond to VEGF by growing into new blood vessels. However, when blood flow in the aortic arches was restricted, mir-126 failed to be expressed. In the absence of this microRNA, new blood vessels were unable to develop due to a block in VEGF signaling. "We have known for over a hundred years that blood flow makes new vessels grow," said Dr. Lawson. "But we never really knew how cells in a growing vessel interpreted this signal.
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