The way human body parts communicate with each other, especially when it comes to disease, is a still mystery. It’s a puzzle Stephen Chan has been trying to solve.
“We primarily define diseases based on where the originating events are occurring. For example, if someone is having a heart attack, you most often presume the problem is the heart,” said Chan, director of the Vascular Medicine Institute at the University of Pittsburgh. “But we are still learning about many different and surprising ways that separate body parts communicate with one another. So, signals from very separate and distinct organs of the body could in fact be the root causes of diseases of the heart and lung.”
For more than a decade, unproven theories have percolated about tiny molecules called microRNAs that circulate in the bloodstream. Proof has been elusive as to whether they can act as long-range messengers between organ systems in living subjects and control important processes of human health and disease.
However, Chan and his team at Pitt and France have confirmed that hypothesis with a paper published today in the latest print issue of Circulation Research. Chan, a professor of medicine, is also director of the Center for Pulmonary Vascular Biology and Medicine.
The team tracked microRNA movement among blood systems in mice and showed that they can travel long distances throughout the body to influence disease development. Namely, Chan’s team found that microRNAs formed out of bone marrow and were transported to the inner lining of the blood vessels of the lung, promoting pulmonary hypertension—a deadly disease that currently has no cure.
“We found definitive proof that microRNAs can function very much like hormones in our bloodstream,” Chan said. “It opens the door to a whole new way of looking at how the body senses and communicates.”
For pulmonary hypertension, Chan said that doctors can now potentially develop treatment strategies aimed at tracking and modulating microRNAs in the blood—a part of the body much more accessible than trying to deliver therapies to the lung.
But the study’s implications go far beyond this single disease.
“Perhaps this is also how the body ‘talks’ to tumors in cancer or how the brain converses with the heart,” Chan posits.
“This study achieves importance as it has broad applicability to a great number of other disease states where endocrine delivery of microRNAs has been suggested to be the linchpin mechanism,” said Jane Leopold, associate professor of medicine at Harvard Medical School and author of the paper’s editorial. She was part of the journal’s committee who reviewed the paper.
Chan also said he is interested in studying circulating microRNAs in physiological functions, such as exercise.
“Exercise is the ultimate example of how all parts of the body must sense and work together intimately and in sync. MicroRNAs circulating in our blood could serve as the conduit that binds it all together.”
Other Pitt researchers directly involved with the study include Partha Dutta, assistant professor of medicine in cardiology division; Prithu Sundd, assistant professor of medicine and bioengineering; Michael Risbano, assistant professor of medicine and director of the Advanced Cardiopulmonary Exercise Testing (ACPET) Program; and Seyed Nouraie, associate professor of medicine. In France, Thomas Bertero acted as a principal investigator at Université Côte d'Azur.