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Research from Children's Hospital Boston suggests that a urine test can help in both monitoring and predicting // vascular anomalies. The study also raises the possibility of treating these with anti-angiogenesis drugs

The July issue of the journal - Pediatrics, has published an article about vascular anomalies in children. Vascular anomalies can be found in about 10% of newly born infants and include both vascular malformations and vascular tumors.

These occur when the cells lining blood vessels multiply abnormally, forming clusters of vessels and then they are also called – Hemangiomas. They can grow rapidly in the first year of life, then usually shrink and disappear. But some grow quite large, causing obstruction, ulceration and other problems.

Marsha Moses, PhD of Children's Vascular Biology Program, senior investigator on the study, had been studying the matrix metalloproteinases (MMPs), a family of enzymes required for angiogenesis, or growth of new blood vessels.

Angiogenesis is also critical to a cancer's expansion, and Moses' lab was the first to show that inhibitors of MMP can inhibit angiogenesis. Recently, her lab also demonstrated that cancer patients have elevated levels of MMPs in their urine. Because vascular anomalies like hemangiomas also involve angiogenesis.

Moses, Marler and colleagues tested the urine of 217 patients with vascular anomalies and 74 healthy controls of the same age and tested it for MMP . A subgroup of MMPs – known as the high-molecular-weight MMPs – were elevated in the urine of 53 percent of patients with vascular tumors and 41 percent of those with vascular malformations, but in only 22 percent of controls.

Vascular anomalies were also associated with elevated urine levels of basic fibroblast growth factor (bFGF), another compound that promotes angiogenesis. Increased urine levels of MMPs and bFGF correlated with both the extent and progression of vascular anomalies. The new findings suggest, for the first time, that angiogenesis also plays a role in the progression of vascular malformations, raising the possibility of curbing these difficult-to-treat anomalies with anti-angiogenic drugs, in particular MMP inhibitors.

Current treatment for vascular malformations consists of surgery, embolization or sclerotherapy, which can be dangerous, deforming, or produce unsatisfactory results.

Children's Hospital Boston researchers have in 1980 already showed that growth of hemangiomas is known to be angiogenesis-dependent and can be suppressed with anti-angiogenic drugs –currently, corticosteroids and vincristine. "Prior to this study, we had thought it was not possible to treat vascular malformations with drugs, since congenital anomalies generally do not respond to drugs," says Steven Fishman, MD, a surgeon on Children's Vascular Anomalies team. "This study gives us hope that with further research we'll be able to develop drug treatments."

Urine testing for MMPs may help physicians know when a vascular anomaly is about to become aggressive and needs intervention. "It can be very hard to tell whether an anomaly will progress," Fishman says. "It can sit there and do nothing, or go on to destroy the nose or other nearby tissues. What we've shown that the presence of MMPs in urine correlates with how aggressive the lesions are."

News Extract from - http://www.childrenshospital.org/research/. Contact: Elizabeth Andrews elizabeth.andrews@childrens.harvard.edu 617-355-6420 Children's Hospital Boston
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