Scientists from the Gladstone Institute of Cardiovascular Disease (GICD) and UCSF have identified a key regulatory factor that controls development of the human vascular system, the extensive network of arteries, veins, and capillaries that allow blood to reach all tissues and organs.
The research, published in the latest issue of Developmental Cell, may offer clues to potential therapeutic targets for a wide variety of diseases, such as heart disease or cancer, that are impacted by or affect the vascular system.
Researchers in laboratory of GICD Director Deepak Srivastava, MD, found that microRNA (miR-126), a tiny RNA molecule, is intimately involved in the response of blood vessels to angiogenic signals. Angiogenesis, the process of vascular development, is a tightly regulated and well-studied process.A cascade of genes orchestrate a series of events leading to formation of blood vessels in an embryo.
"Some of these same gene regulatory networks are re-activated in the adult to direct the growth of new blood vessels" said Jason Fish, PhD, lead author of the study. "This can be beneficial, as in the case of a heart attack."
Blood vessel formation can also contribute to disease in settings like cancer, where vessels feed a growing tumor.
"Finding that a single factor regulates a large part of the angiogenic process creates a significant target for therapeutic development for any disease involving the vascular system," said Dr. Srivastava. "The next step is to find ways to modify this microRNA in the setting of disease and test its ability to alter the disease process."
Researchers examined cells, called endothelial cells, that line the lumen or inside of blood vessels. Once the vascular endothelial cells adopt their fate during development, they come together to form cord-like structures that are remodeled to become lumenized blood vessels. In adults, angiogenic signals, such as vascular endothelial growth factor (VEGF), activate endothelial cells and cause them to form new blood vessels. Individual microRNAs, which titrate the level of specific proteins generated by the cell, were not previously known to affect VEGF signaling or regulate angiogenesis.