Vanderbilt University researchers have found a genetic mutation that causes pulmonary hypertension in cattle grazed at high altitude, and which leads to a life-threatening condition called brisket disease. Their findings, reported online on April 15, 2015 in an open-access article in Nature Communications, may shed light on human lung disease, in particular, the mechanism behind non-familial pulmonary hypertension in patients with conditions such as emphysema and pulmonary fibrosis. "A genetic variant in cattle might tell us why some humans get into trouble at sea level and at altitude," said first author John H. Newman, M.D., the Elsa S. Hanigan Professor of Pulmonary Medicine at Vanderbilt University Medical Center. When the lung experiences low oxygen, or hypoxia, the blood vessels of the lung constrict. Over time in continued hypoxic conditions, these vessels become muscularized, resulting in pulmonary hypertension, high blood pressure in the blood vessels of the lung. Lowland cattle can develop pulmonary hypertension after being at high altitude over a period of six months to a year. Brisket disease, or right heart failure, develops when the heart fails to pump against the high pulmonary blood pressure. If these animals are not brought to lower altitudes, they will die. Brisket disease costs millions of dollars of loss each year in the Rocky Mountains, where the herds graze. Fifteen years ago, Dr. Newman, James Loyd, M.D., Rudy W. Jacobson Professor of Pulmonary Medicine, and colleagues identified the genetic basis for familial pulmonary hypertension in humans, mutations in a gene called BMPR2 (bone morphogenic protein receptor type 2). "I was sitting in our conference room after we had found the BMPR2 gene in humans and I thought, well, we should be able to find the brisket gene in cattle using the same strategy," Dr. Newman said.
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