Cattle research may provide lung disease clues

Chuck Bednar for – @BednarChuck

The discovery of a genetic mutation that can cause pulmonary hypertension in cattle grazed at high altitudes could shed new light on lung diseases affecting humans, according to new research published earlier this week in the journal Nature Communications.

The variant, which leads to a life-threatening condition known as brisket disease in cattle, could help uncover the mechanisms behind non-familial pulmonary hypertension in patients that have conditions emphysema and pulmonary fibrosis.

How altitude can cause hypertension in the lungs

The newly discovered genetic variants in cattle could help explain why some people struggle at sea level and higher altitudes, John Newman, Elsa S. Hanigan Professor of Pulmonary Medicine at VU and first author of the study, explained Wednesday in a statement.

When the lung experiences the phenomenon known as hypoxia, or deprivation of oxygen supply, the blood vessels of the lung constrict. Over an extended period of time in these conditions, those blood vessels become muscularized, causing high blood pressure or hypertension in the lung.

Lowland cattle can develop pulmonary hypertension after being at high altitude over the course of six to 12 months, they added, and brisket disease (right heart failure) develops when the heart fails to pump against the high pulmonary blood pressure. The condition is fatal unless the cows are moved to lower altitudes, and this causes millions of dollars worth of cattle to die each year.

“About 20 percent of cattle moved from lowland herds to high plains pastures develop high altitude pulmonary hypertension – they get short of breath, and eventually have right heart failure if it’s not caught and the cattle returned to low altitude,” Dr. James West, an associate professor of medicine at Vanderbilt co-author of the study, told redOrbit via email. “It’s called brisket disease because the heart failure leads to edema and swelling in the brisket region.”

Discovering the genetic causes of brisket disease in cattle

Dr. Newman was part of a VU team that first identified mutations in a gene called BMPR2 that act as the genetic basis for familiar pulmonary hypertension in humans 15 years ago. Shortly after that discovery, he said that he predicted that they would be able to use the same approach to find the gene responsible for causing brisket disease in cattle.

He and his Vanderbilt colleagues joined forces with Timothy Holt of Colorado State University, an expert on brisket disease, to seek out the genetic causes of the disorder. Hold evaluated herds of cattle for pulmonary hypertension and sent blood samples to VU, where DNA was extracted and analyzed.

The researchers found that the majority of the cattle with high-altitude pulmonary hypertension had a double mutation in the gene HIF2alpha, which expresses hypoxia inducible factor. At low altitudes, this protein is constantly degraded and has no effect on the cattle. However, it activates in a hypoxic environment in order to help battle the physiological effects of low oxygen.

Brisket disease “has been a problem throughout the history of high plains cattle ranching, and has been studied intensively for more than fifty years,” Dr. West told redOrbit. “This study shows that the problem is mostly, but not entirely, linked to a variant in an oxygen sensing gene, which causes the animals to have excessive reaction to the lower oxygen levels at high altitude.”

“Since it’s a simple variant, it can be easily added to the battery of variants many cattle producers already use to test for genetically known traits in their herds – it will cost cattlemen essentially nothing to add this to the list of traits they know about their cattle, and can potentially save them money by keeping their cattle healthy,” he added.

Raising the ‘steaks’: Benefits for all

The mutation discovered in the cattle makes the protein resistant to degradation, the researchers discovered, leading to excessive pulmonary hypertension. The VU group is now developing a new test that will help ranchers determine which cows have this mutation so that they can keep those cattle from being transported to higher altitudes.

The study, which was supported in part by grants from the National Institutes of Health, could reduce the prevalence of brisket disease and prevent costly losses of stock. In addition, it might be beneficial in treating ailments caused by a similar variant in humans, the authors noted.

“We’ve actually done a little preliminary looking for whether or not variants in this gene is an issue in human pulmonary hypertension,” Dr. West explained to redOrbit via email. “It looks like it may be an issue in humans extremely rarely, and so in a personalized medicine sense it could be important for those specific patients, but more broadly understanding that this is part of how lungs adapt to lowered oxygen will be important to preserving health in humans with lung diseases like COPD.”


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