New method to grow arteries could lead to 'biological bypass' for heart disease

New Haven — A new method of growing arteries could lead to a "biological bypass" — a non-invasive way to treat coronary artery disease — Yale School of Medicine researchers and their colleagues report in the April issue of the Journal of Clinical Investigation.

Coronary arteries can become blocked with plaque, leading to a decrease in the supply of blood and oxygen to the heart. Over time this blockage can lead to debilitating chest pain or heart attack. Severe blockages in multiple major vessels may require coronary artery bypass graft surgery, a major invasive surgery.

"Successfully growing new arteries could provide a biological option for patients facing bypass surgery," said lead author of the study, Michael Simons, MD, chief of the Section of Cardiology at Yale School of Medicine.

In the past, researchers used growth factors  and proteins that stimulate the growth of cells — in an attempt to grow new arteries, but this method was unsuccessful. Simons and his team studied mice and zebrafish to see if they could simulate arterial formation by switching on and off two signaling pathways: ERK1/2 and PI3K.

"We found that there is cross-talk between the two signaling pathways. One half of the signaling pathway inhibits the other. When we disable the inhibitor mechanism, we are able to grow arteries," said Simons. "Instead of using growth factors, we stopped the inhibitor mechanism by using a drug that targets a particular enzyme called PI3-kinase inhibitor."

"Because we've located this inhibitory pathway, this opens the possibility of developing a new class of medication to grow new arteries," Simons added. "The next step is to test this finding in a human clinical trial."

Other authors on the study included Bin Ren, Yong Den, Arpita Mukhopadhyay, Anthony A. Lanahan, Zhen W. Zhuang, Karen L. Moodie, Mary Jo Mulligan-Kehoe, Tatiana V. Byzova, and Randall T. Peterson.

Yale New Haven Hospital (YNHH), part of Yale New Haven Health, is a nationally recognized, 1,541-bed, not-for-profit hospital serving as the primary teaching hospital for the Yale School of Medicine (YSM). Founded as the fourth voluntary hospital in the U.S. in 1826, today, YNHH has two New Haven-based campuses, and also includes Yale New Haven Children's Hospital, Yale New Haven Psychiatric Hospital and Smilow Cancer Hospital. YNHH has received Magnet designation from the American Nurses Credentialing Center, the nation’s highest honor of nursing excellence. YNHH has a combined medical staff of about 4,500 university and community physicians practicing in more than 100 specialties. www.ynhh.org