Scientists have discovered how heart disease patients with dangerously blocked arteries are able to grow new blood vessels to by-pass the blockage, and keep oxygen-rich blood flowing through their bodies. The discovery is raising the possibility of new treatments for cardiac patients.
In people with heart disease, it is not uncommon for new blood vessels to grow around blocked arteries in order to keep essential, oxygenated blood coursing through the body. But those emergency blood vessels don’t grow in everyone with coronary artery disease.
Researchers have been working for more than a decade trying to coax new blood vessel formation, or angiogenesis, using human growth factors, specific enzymes and hormones that promote cellular growth.
But Michael Simons, a cell biologist and head of cardiovascular research at Yale University in New Haven, Connecticut, says scientists found that growth factors only went so far in stimulating new blood vessel growth.
“They do that in normal animals and in normal people. But they did not work in people with advanced illnesses, and we never understood why,” said Simons.
Simons and colleagues took a step back, looking at factors that cause blood vessels to form during fetal development, to try to determine why that process often doesn’t occur in people with advanced heart disease.
When organs are damaged because of a lack of blood flow, Simons explains, they release a repair molecule called VEGFR. Another molecule called NRP1 binds to that protein, and transports it, along with a second repair protein called VEGFR2, to the inside of blood vessels, stimulating the healing process.
But in experiments with mice, researchers discovered repair doesn’t take place, or is poorly executed, in rodents bred to have damaged NRP1. Simons says angiogenesis is hampered because the molecules can’t enter damaged blood vessels.
Simons believes heart patients whose bodies do not repair and grow new arteries to bypass damaged blood vessels also have impaired NRP1.
“So, now that we understand how this works, you can now begin designing therapies that will specifically stimulate this pathway where you need it if you want to grow arteries. On the other hand, if your goal is to inhibit the growth of blood vessels, you could do this of course in reverse,” he said.
Reversing blood vessel formation would choke off and destroy cancerous tumors, which require an arterial blood supply to grow and spread.
An article by Yale University’s Michael Simons and colleagues on blood vessel formation is published in the journal Developmental Cell.