A form of specialized muscle cells surrounding capillaries, called a pericyte, has been discovered to play a role in initiating angiogenesis, or blood vessel growth, according to researchers at Tufts University School of Medicine (TUSM) and the Massachusetts Institute of Technology (MIT). The study, published in Journal of Physics: Condensed Matter, suggests that these cells use mechanical forces to initiate “sprouting” of new blood vessels, a new discovery in the angiogenesis field. 

Previously, scientists have focused on the chemical signals that initiate angiogenesis and have developed drugs, known as angiogenesis inhibitors, to impede these signals in cancerous tumors and in blinding diseases, such as age-related macular degeneration. Now, it appears that the mechanical signals from pericytes can also play a role in regulating angiogenesis.

The researchers isolated pericytes and placed them to a silicone membrane. With an atomic force microscope, researchers at MIT measured the stiffness of the contracting pericytes and the consequent degree of wrinkling the pericytes caused in the membrane. Pericytes generated contractions that caused underlying membranes to shorten by an average of 38%.

“This collaboration enabled us to quantify the role that mechanics plays in angiogenesis at the cellular level,” said co-senior author Krystyn J. Van Vliet, PhD, associate professor of materials science and engineering at MIT. “These measurements allowed us to estimate how much pericytes contracted and stiffened the microvascular environment, sending mechanical signals to nearby cells.”

“In the body, such local contractions could serve as the initiating, mechanical signals that influence angiogenesis,” said co-senior author Ira Herman, PhD, professor of physiology at TUSM. “If we find that mechanical signaling, such as the force exerted by pericytes, initiates angiogenesis, we can explore ways of interfering with these signals.

According to William W. Li, M.D., president and medical director of the Angiogenesis Foundation, “Some antiangiogenic drugs already in use, such as sunitinib (Sutent) and sorafenib (Nexavar) already target a growth factor, PDGF, involved in pericyte function. This new discovery may help to explain how these treatments work, and suggest ways to improve the next generation of therapies for cancer and other diseases.”