A team led by SFVAMC vascular surgeon Rajabrata Sarkar, MD, PhD, has demonstrated in mice that the MMP2 gene is essential for the growth of new arteries when the femoral (leg) artery is blocked.
The team also identified and described, for the first time, the specific DNA sequences of the MMP2 gene that are expressed when new arteries are grown.
The study appears in the November 8 issue of the Proceedings of the National Academy of Sciences.
"It is not clear why some patients grow new arteries in response to an arterial blockage and others do not," observes Sarkar, who is also an assistant professor of surgery at the University of California, San Francisco. "So it's very important to understand the normal process that allows an animal or a person to grow new arteries when their legs don't get good blood flow. Legs are a big problem, because if you don't have enough blood flow, it can eventually lead to gangrene and amputation."
In the first part of the study, Sarkar and his group mimicked human vascular disease in the femoral arteries of normal mice and of mice that lacked the MMP2 gene, which encodes an enzyme that promotes the growth of new arteries.
The normal mice grew new arteries, and in about three weeks the blood flow in their legs was close to normal.
The mice without the MMP2 gene did not grow new arteries. About 40 percent lost a portion of a leg due to gangrene caused by inadequate blood flow, demonstrating that the MMP2 gene is "very important" in an animal's ability to grow new arteries in response to a blockage, says Sarkar.
The second part of the study looked at precisely which areas of the MMP2 gene are activated in skeletal muscles where blood flow is decreased.
The researchers mimicked arterial blockage in transgenic
Source:University of California - San Francisco