Protein Controls Blood Vessel Formation, Offers New Drug Target

After an injury, the body grows new blood vessels to repair damaged tissue. But sometimes too much growth causes problems, as when new blood vessels in the eyes leak, causing diabetic retinopathy and blindness if not treated.

A protein called CIB1 discovered by researchers at the University of North Carolina at Chapel Hill School of Medicine appears to play a major role in controlling new blood vessel growth, offering a target for drug treatments to help the body repair itself after injury and control unwanted blood vessel growth.

“In the future, this knowledge may help our ability to control blood vessel growth in disease situations such as wound healing, retinal diseases and diabetes,” said Leslie Parise, Ph.D., senior study author and professor and chair of biochemistry and biophysics in the UNC School of Medicine.

The results will appear in an upcoming print issue of the journal Circulation Research and were published online Nov. 1, 2007. The research was funded by the National Institutes of Health.

Parise’s lab first discovered the protein, called CIB1 in 1997. It was originally found in blood platelets. CIB1 keeps blood platelets from sticking together, acting as a natural anti-coagulant to prevent clots that might lead to heart attacks or strokes. But further research showed CIB1 appears in almost every cell type in the body, Parise said. For example, male mice bred without both copies of the CIB1 gene are infertile.

In the current study, Parise and her colleagues found CIB1 in the endothelial cells that line all blood vessels. These cells jump-start new blood vessel growth via a process called angiogenesis. During angiogenesis, biological signals prompt endothelial cells to release enzymes and other chemicals that allow them to move away from existing blood vessels and form new ones.

While angiogenesis plays a critical role in embryo growth, CIB1 appears to only affect blood vessel growth after injury (sometimes called pathological or adaptive angiogenesis). Mice born without copies of the CIB1 gene survive and are reasonably healthy unless injured, Parise said.

“CIB1 appears to be an attractive drug target to control blood vessel growth since it does not play an essential role during fetal development but instead plays an important role in pathological forms of blood vessel growth,” said first author and medical student at UNC Mohamed Zayed, Ph.D.

In experiments in mice missing CIB1 genes, the researchers found that CIB1 is critical for angiogenesis in the retina, as well as angiogenesis in hind legs. In both cases, the new blood vessel growth was prompted by ischemia, or restricted blood flow. However, clinicians treating retinal disease need to restrict blood vessel growth in the eyes, while patients with restricted blood flow in their limbs need to grow need blood vessels. Therefore, CIB1 could be a target for both pro- and anti-angiogenic drug therapies.