Development of the various components of the human body, including organs, bones, and blood vessels, occurs through processes directed by certain genes. These genes signal cells and tell them where to go, what to do, and how to get there. For the formation of blood vessels, including veins, these cells are directed to form two types of tissue: the endothelium, which is a layer of cells lining the interior of blood vessels; and smooth muscle tissue, which surrounds the endothelium. Signals from certain genes are needed to properly form the endothelium in the right shape, and the smooth muscle tissue in the right amount – more for arteries, less for veins – and thus to form normal, functional blood vessels.

Vascular anomalies form when these cells do not receive the proper signals. Blood vessels form in the wrong place, in the wrong size, and with the incorrect relationship between the endothelium and the smooth muscle tissue around the blood vessels. Anomalies can be as small as simple birthmarks that many people have, or can grow into large tangles of blood vessels that can grow, disfigure, and even become fatal.

The most common form of vascular anomaly is the venous malformation, which are deforming growths that enlarge with age and can invade neighboring tissues in a person's body. They can occur sporadically, or be hereditary and appear at birth or later in life. The researchers on this project have discovered a gene linked to these hereditary malformations. This gene, which is responsible for directing normal growth of blood vessels – telling cells how to grow, where to grow, and in what quatities – can also, when mutated, be responsible for the growth of venous malformations.

This gene was originally identified and sequenced by the researchers in the Olsen Lab, who are also the Principal Investigators on this new project. Through mapping the genes of two families with hereditary venous malformations, they were able to identify the gene, called TIE-2 and located on chromosome 9, and to sequence it. They discovered that in individuals suffering from veinous malformations, the sequence of the TIE-2 gene differed from the normal by only a single nucleotide. Then, in a controlled experiment, researchers in the Olsen Lab, in collaboration with the Cantley Lab at the Harvard Medical School, inserted two versions of the gene (one normal, one mutated) into insect cells. The cells with the mutated gene exhibited a significantly higher level of signaling for vein growth than those without the mutation. This increased signaling is believed to then alter the characteristics of the endothelium, and thus influence the growth of venous malformations. Further study of unrelated families which also exhibited hereditary venous malformations, turned up evidence of the same mutation on the TIE-2 gene on chromosome 9, and the same hyperactivity in the signaling of blood vessel growth.

The goal now is to further explain the problems with this increase in signaling, and to hopefully develop new methods of treatment for venous malformations, which will be more effective than current treatments.

Click here to read more about this study in particular.

More Background Articles:

Harvard University Gazette Article - "When a Birthmark is Born: Researchers find that unique marks are based on genetics", 3/27/1997
http://www.hno.harvard.edu/gazette/1997/03.27/WhenaBirthmarki.html