This duality could make both angiogenesis-promoting and angiogenesis-suppressing drugs ineffective in preventing renarrowing of arteries following angioplasty or stenting. "In fact, pro-angiogenic drugs could make things worse, not better," Simons said. "If you're going to use an angiogenic agent, it will do harm, because it will actually promote stenosis [narrowing] instead of inhibiting it."
The studies were done in rabbits, chosen for their thick human-like arteries. Using an agent to stimulate angiogenesis on the outer surface after local injury, the researchers found a large increase in smooth muscle in the inside lining of the artery, meaning that angiogenesis induced intimal growth that narrowed the blood vessel. Then, using different agents to inhibit angiogenesis, they showed that even when angiogenesis was completely stopped, some new muscle accumulated.
"Intimal growth is a fundamental pathology responsible for many cardiovascular diseases including atherosclerosis and hypertension," Simons said. "This is the first time such a combination of angiogenesis-dependent and independent phases of smooth muscle growth has been proposed."
Study co-authors are Dr. Rohit Khurana, who was a visiting Fulbright scholar from University College London, Dr. Zhenwu Zhuang, Dr. Masahiro Murakami, and Dr. Ebo De Muinck, all from Dartmouth Medical School, as well as colleagues from London, Finland and Genent
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Contact: Andrew Nordhoff
mednews@dartmouth.edu
603-650-1492
Dartmouth Medical School
11-Oct-2004