Researchers have discovered that a developmental anticancer agent has the ability to support regeneration in damaged heart tissues, opening up a possible new treatment option for heart disease.
In a study published in the journal Proceedings of the National Academy of Sciences, Lawrence Lum and colleagues detailed their discovery, outlining their work on a cancer drug targeting Wnt signaling molecules.
These molecules are necessary for regenerating tissues but also have a role in cancer development, and essential to Wnt protein production in people is the porcupine (Porcn) enzyme. It was while they were trying to inhibit the Porcn enzyme that the researchers discovered their cancer drug's surprising effect.
"We saw many predictable adverse effects ... but one surprise was that the number of dividing cardiomyocytes was slightly increased," said Lum, the study's senior author.
Studying Wnt Proteins
For the study, the researchers induced heart attacks in mice, administered a Porcn inhibitor as treatment, and observed that the mice hearts' blood-pumping ability had improved by almost twofold compared to subjects that were left untreated.
Rhonda Bassel-Duby, Hamon Center for Regenerative Science and Medicine's associate director and one of the study's authors, said it was striking to see that administering a Wnt inhibitor could significantly improve heart function after a heart attack.
Heart Repair Effects
Aside from improved blood-pumping ability, the hearts of treated mice also showed reduced fibrosis, or scarring. When an abundance of collagen is present, heart scarring can cause the organ to dramatically increase in size, leading to heart failure.
Lum explained that fibriotic responses can have immediate benefits but they can also overwhelm the heart's regeneration ability in the long run. With the drug agent they are developing, he and the rest of the research team believe that they can regulate fibriotic response, which will improve the heart's wound-healing abilities. The Porcn inhibitor will also only require a short usage duration so it may be possible as well to avoid the unpleasant side effects usually attributed to cancer drugs.
The researchers are hopeful that they'll be able to conduct clinical trials next year on the Porcn inhibitor to confirm its potential as a regenerative aid for heart disease.
Lum and Bassel-Duby were joined by Jesung Moon, Eric N. Olson, Huanyu Zhou, James F. Amatruda, Li-shu Zhang, Noelle S. Williams, Wei Tan, Jian Q. Feng, Ying Liu, Sean P. Palecek, Shanrong Zhang, Xiaoping Bao, and Lorraine K. Morlock in the research.
Heart Disease Statistics
According to the American Heart Association's Heart Disease and Stroke Statistics Update for 2017, cardiovascular disease remains the leading cause of death in the United States, with about 6.5 million American adults suffering from heart failure from 2011 to 2014. The AHA's report also projects this figure will increase by 2030 by 46 percent. Heart failure is defined as a condition where the heart is too weak to normally pump blood through the body.
According to the U.S. Centers for Disease Control and Prevention, some 735,000 Americans experience heart attacks each year. Out of all the heart disease types, coronary heart disease is the most common, claiming more than 370,000 people annually.
