Healing heart tissue by coaxing small arteries to grow

Some patients with blockages in the heart's major arteries can still lead normal lives, basically performing all their everyday activities with no major limitations posed by their disease. But how?

Joseph Woo, a professor of cardiothoracic surgery at Stanford University, figured it may be because those people have tiny arteries that bypass blood clots to reach the heart. Now Woo, along with biologist Kristy Red-Horse and colleagues, has shown that a protein promotes the growth of arteries and helps heal damage caused by heart disease.

The protein is called CXCL12, and it is expressed in many tissues. Scientists believe it plays a key role in the formation of new blood vessels. When injected in adult mice, CXCL12 helped grow collateral arteries leading to injured hearts, the Stanford-led team reported in a study published in the journal Cell.

The scientists started their research using newborn mice. “Neonatal mice have a robust ability to heal injured heart tissue, but they no longer have that ability in adulthood,” Red-Horse said in a statement. “Understanding why could identify ways of reigniting regeneration in adults.”

When they looked at the hearts of newborn mice at the cellular level, they found that arterial endothelial cells—which form the inner lining of blood vessels—would leave the artery, migrate along capillaries and reassemble to form collateral arteries at injured regions. They then hypothesized that CXCL12 could have played a part in this process.

CXCL12 has been shown to improve cardiac recovery after heart attacks. In their study, Woo, Red-Horse and their colleagues discovered that CXCL12 exists mostly in arterial endothelial cells in healthy neonatal mice. When oxygen levels run low in injured areas of the heart, genes that express CXCL12 turn on, and endothelial cells migrate towards the damaged tissue.

The scientists wondered if they could produce the effect in adult mice by administering CXCL12. After injecting the protein in damaged areas, many new collateral arteries indeed formed in the adult animals. No new arteries were observed in mice that didn't receive the protein, the team reported.

RELATED: Targeting heart disease by focusing on a protein that dilates blood vessels

Helping blood vessels maintain or restore their normal function is a strategy that cardiologists are exploring to fight heart disease. Scientists at the Scripps Research Institute, for example, recently found that a protein called FPR68 can dilate arterioles and potentially relieve high blood pressure or prevent blood vessel blockage.

Woo and Red-Horse suspect there’s more to the story of arterial endothelial cell migration than just CXCL12. Still, they hope their findings could offer the basis for a new therapy that induces collateral artery growth in human. “The question now is whether this mechanism we have discovered can be manipulated therapeutically to generate collateral arteries in human patients,” Woo said.