Molecular Regulator for Blood Flow Found in Mice

“NO is a well-studied signaling molecule already known for its important role in erectile dysfunction and heart disease,” said NCI Director John Niederhuber, M.D. “This finding could have implications for anti-angiogenesis therapies aimed at regulating blood flow into tumors and improving healing after surgery.”

NO is a biologically active gas produced by many different cell types, including the innermost cell layer lining of blood vessels. As NO gas quickly spreads to the underlying smooth muscle cells and halts contraction, blood vessels enlarge and blood flow increases. In this way, NO regulates blood pressure and the distribution of blood throughout the body. By increasing blood flow to tissues, NO acts to offset tissue ischemia — the restriction of the blood supply to tissues and organs. Tissue ischemia is a major cause of tissue damage that is associated with cardiovascular disease and diabetes.

One protein involved in the NO-signaling pathway is called TSP1, or thrombospondin-1. It is a multifunctional protein found on the surface of many cell types. One identified function for TSP1 is restriction of tumor growth by reducing the formation of new blood vessels. TSP1 accomplishes this by counteracting the blood vessel growth-stimulating effect of low concentrations of NO. The development of new blood vessels, a process known as angiogenesis, is essential for providing tumors with a fresh supply of oxygen and nutrients. Widespread loss of TSP1 has been observed in some types of cancer.

“The human body must carefully balance cell signaling pathways. It is important for NO to encourage a limited amount of angiogenesis for wound healing, but this molecular messenger must be regulated, by TSP1 and possibly other proteins, in order to prevent uncontrolled angiogenesis seen in tumor development and other diseases,” explained David Roberts, Ph.D., head of the Biochemical Pathology Section at NCI and senior author of the study.

Extending this work to an injury that deprives skin tissue of blood flow and results in substantial tissue death, the researchers found that mice without TSP1 also showed enhanced tissue survival as compared to normal mice. This finding was attributed to increased angiogenesis and recovery of oxygen levels, important factors in wound repair.

Message posted by: Rashmi Nemade