Scientists have discovered a cell mechanism involving the hormone leptin that plays a key role in the formation of new blood vessels. The discovery may help to develop treatments that stimulate tissue repair following a heart attack, as well as treatments that stop abnormal tissue growth, such as in cancer.
A report on the discovery, by researchers at the University of Bristol in the United Kingdom, is published in the journal Scientific Reports.
The finding reveals important new clues about the cell biology of “angiogenesis,” or the generation of new blood vessels, which occurs in both health and disease.
The researchers, including study leader Paolo Madeddu, a professor of experimental cardiovascular medicine at the University of Bristol, believe that their discovery could help to improve treatments for heart attack and cancer, two of the world’s leading causes of death.
For example, heart attacks damage heart muscle, and a better understanding of how to generate new blood vessels could improve regenerative medicine approaches that help the heart to repair itself.
Similarly, in cancer, tumors rely on the formation of new blood vessels to grow, so understanding how this happens could help to develop treatments that block this growth.
Heart disease, the main cause of heart attacks, is the world’s biggest killer. In 2015, an estimated 17.3 million people died from heart disease and the number is expected to exceed 23.6 million by 2030.
Cancer caused approximately 8.8 million deaths worldwide in 2015. The number of new cases, currently estimated at around 14 million per year, is expected to increase by 70 percent over the next 20 years.
In their report, the researchers note that pericytes are “emerging as promising candidates” for treatments that involve new blood vessel generation.
Studies that have investigated what happens when pericytes are transplanted into tissue that has suffered from insufficient blood supply, or “ischemia,” have already shown that the cells are stimulated by lack of oxygen. However, the molecular process remained unknown.
Prof. Madeddu and colleagues discovered that the hormone leptin appears to play an important role in the ability of pericytes to stimulate new blood vessel growth.
Leptin, a hormone produced by fat cells, is already known to be important for regulation of appetite and energy balance. The authors note that there is also evidence that some components of the leptin “pathway are expressed in human stem cells,” but it is not clear how it works.
The team discovered that when starved of oxygen, pericytes produce 40 times more leptin and that this overproduction continues until oxygen levels return to normal.
The researchers also found that the increase in leptin makes the pericytes more resistant to induced cell death, or “apoptosis,” and that it enhances their ability to migrate and stimulate blood vessel formation.
They conclude that leptin appears to play an important part in a number of actions that help to generate new blood vessels in tissue that has suffered from oxygen starvation.
“Increasing leptin in pericytes in a damaged heart might help it to heal faster,” Prof. Madeddu explains, “whereas blocking the production of leptin in cancerous pericytes might starve the tumor of nutrients and force it to shrink.”
He and his colleagues hope that the discovery will help to develop treatments that mean heart attack patients do not have to undergo coronary artery bypass, which usually takes a long time to recover from.
The invasive surgery involves taking blood vessels from elsewhere in the body, such as a leg, to bypass the damaged artery and restore blood flow to the heart muscle.
“This new discovery could have important implications for the treatment of heart attacks, which is when a main coronary artery gets blocked, but also cancer. These results reveal a new signaling mechanism that may have a far-reaching and significant impact on cardiovascular regenerative medicine.”
Prof. Paolo Madeddu