New Discovery Identifies One Source of Blood Vessel Formation

The findings were published in the February 12, 2004 issue of Nature. The research was led by Qing Wang, Ph.D., director of the Cleveland Clinic’s Center for Cardiovascular Genetics and associate professor, department of molecular cardiology, the Lerner Research Institute.

"This finding is important for several reasons," said Dr. Wang. "First, it provides additional insight into the rare illness we studied to help isolate the angiogenesis gene. Next, it already has shown us how certain processes work within the body to increase or decrease blood vessel growth. Future research will seek to control this growth—either by starting or stopping it—to help control disease."

The growth of new blood vessels is an important natural process, both in health and disease, said Dr. Wang. In many serious disease states, the body loses control over angiogenesis. Excessive angiogenesis, or blood vessel growth, occurs in cancer, age-related macular degeneration, rheumatoid arthritis and more than 70 other conditions. In these conditions, new blood vessels feed diseased tissue and destroy normal tissue. With cancer, angiogenesis nourishes tumor cells with oxygen and nutrients. But in other disorders, such as coronary artery disease, stroke and delayed wound healing, insufficient angiogenesis is part of the problem, contributing to poor circulation and the risk of tissue death.

In their quest to uncover the secrets of blood vessel growth, Dr. Wang and his colleagues studied a rare vascular disease called Klippel-Trenaunay Syndrome (KTS). Klippel-Trenaunay is a circulatory disorder characterized by varicose veins, abnormal thickening of bones and soft tissues, and cutaneous capillary malformations commonly called "purple wine stains."

By studying people with KTS, the team identified the first gene (VG5Q) associated with an increase in the risk for development of KTS. The gene appears to be linked to about 4 percent of KTS patients. Identification of the gene will help physicians make a definitive diagnosis in certain cases, said Dr. Wang, which is important because KTS shares similar traits with several other vascular conditions.

During their research, the team found that:

• KTS patients with mutations of the VG5Q gene experienced increased blood vessel formation
• purified VG5Q protein is a potent angiogenic factor that promotes angiogenesis
• blocking VG5Q expression prevents blood vessel formation.

This new knowledge may impact the development of therapeutic strategies aimed at regulating blood vessel growth. Several angiogenic factors already have been brought to clinical trials to treat patients with myocardial or peripheral ischemia and cancer.