Hidden origins of pulmonary hypertension revealed by network modeling

June 24, 2014

In a groundbreaking study, researchers from Brigham and Women's Hospital (BWH) have identified a related family of molecules believed to be a major root cause of pulmonary hypertension, a deadly vascular disease with undefined origins. This is one of the first studies to leverage advanced computational network modeling to decipher the molecular secrets of this complex human disease.

The study is published online June 24, 2014 in The Journal of Clinical Investigation.

Despite the rising number of people diagnosed with the disease worldwide, has been a historically neglected disease. It occurs when there is increased pressure in the blood vessels of the lung, thus compromising the delivery of blood and oxygen to the body. Symptoms are debilitating and include shortness of breath and fatigue, but can progress to heart failure and death.

"Pulmonary hypertension is an example of a so complex that traditional methods of research have failed to provide adequate treatments to prevent or halt its progression," said Stephen Y. Chan, MD, PhD, BWH Divisions of Cardiovascular Medicine and Network Medicine, senior corresponding author. "We have been advancing the idea that mathematical models of this disease can be generated to perform high-volume, systematic analyses that are not feasible with standard experimentation. In doing so, we can make predictions regarding critical molecular networks that underlie the of pulmonary hypertension that have not been possible to this point."

Chan and colleagues have focused on the study of microRNAs, which are small, non-coding nucleic acid molecules that can block production of numerous proteins in human cells with implications in health and disease. With the help of sophisticated computational analyses, the researchers developed a unique molecular model tracing the architecture interconnecting the network of genes and microRNAs associated with pulmonary hypertension.

"Historically, most computational approaches in the study of human disease gene networks go no further than theoretical predictions," said Thomas Bertero, PhD, BWH Division of Cardiovascular Medicine, lead study author. "We wanted to be sure that our predictions were truly valid in real instances of pulmonary hypertension."

Consequently, the researchers confirmed their mathematical predictions with experiments using a wide range of pre-clinical and human models. In doing so, the researchers identified the microRNA family, miR-130/301, as a master regulator of diverse target genes and additional microRNAs, ultimately orchestrating a global proliferative response in diseased leading to pulmonary hypertension.

"This is the first microRNA family found to regulate such a diverse number of pathways specific for pulmonary hypertension, and these molecules could be very effective therapeutic targets for treating this deadly disease," said Chan. "Since all of these findings were previously missed by conventional experiments, our efforts also provide great support for using network modeling to discover the molecular origins of other complex human diseases."

Explore further: First guidelines for patients with pulmonary hypertension in sickle cell disease

Related Stories

First guidelines for patients with pulmonary hypertension in sickle cell disease

March 18, 2014
Boston Medical Center (BMC) and Boston University School of Medicine (BUSM) physicians have helped create the first set of clinical guidelines for treating patients with pulmonary hypertension in sickle cell disease. Elizabeth ...

Pulmonary hypertension deaths have increased over past decade, according to CDC report

April 3, 2014
Deaths from pulmonary hypertension have increased over the past decade, according to a study from the Centers for Disease Control and Prevention (CDC).

The American College of Chest Physicians releases updated PAH guidelines

June 17, 2014
The American College of Chest Physicians (CHEST) announced today the Online First publication of Pharmacological Therapy for Pulmonary Arterial Hypertension in Adults: CHEST Guideline in the journal Chest. Pulmonary arterial ...

Opsumit approved for pulmonary arterial hypertension

October 23, 2013
(HealthDay)—Opsumit (macitentan) has been approved by the U.S. Food and Drug Administration to treat adults with pulmonary arterial hypertension, a debilitating disease characterized by high blood pressure in the lung arteries.

By zooming in on arteries, researcher gets to the root of pulmonary hypertension

February 27, 2014
You might think building muscle is a good thing, but that's often not so in the case of blood vessels in adults. In fact, excess smooth muscle is a root problem in many vascular diseases, as it causes arteries to constrict ...

Blocking molecular pathway reverses pulmonary hypertension in rats

August 28, 2013
Pulmonary hypertension, a deadly form of high blood pressure that develops in the lungs, may be caused by an inflammation-producing molecular pathway that damages the inner lining of blood vessels, according to a new study ...

Recommended for you

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

Engineered liver tissue expands after transplant

July 19, 2017
Many diseases, including cirrhosis and hepatitis, can lead to liver failure. More than 17,000 Americans suffering from these diseases are now waiting for liver transplants, but significantly fewer livers are available.

Lunatic Fringe gene plays key role in the renewable brain

July 19, 2017
The discovery that the brain can generate new cells - about 700 new neurons each day - has triggered investigations to uncover how this process is regulated. Researchers at Baylor College of Medicine and Jan and Dan Duncan ...

New animal models for hepatitis C could pave the way for a vaccine

July 19, 2017
They say that an ounce of prevention is worth a pound of cure. In the case of hepatitis C—a disease that affects nearly 71 million people worldwide, causing cirrhosis and liver cancer if left untreated—it might be worth ...

Omega-3 fatty acids fight inflammation via cannabinoids

July 18, 2017
Chemical compounds called cannabinoids are found in marijuana and also are produced naturally in the body from omega-3 fatty acids. A well-known cannabinoid in marijuana, tetrahydrocannabinol, is responsible for some of its ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.