Dangerously high blood pressure in the lungs, a condition called pulmonary hypertension, occurs when cells that line pulmonary arteries change in an abnormal way. These abnormal cells clog pulmonary arteries raising the blood pressure in the lungs to potentially lethal levels.
Currently, as described in a 2010 Stanford Medicine article, treatment options are limited. And until recently, the cause of these cell abnormalities was unclear. Now, a Stanford-led study of pulmonary hypertension in rats suggests that the abnormal cells that narrow or block pulmonary arteries are caused by an inflammation-producing molecular pathway.
We believe this is going to be an approach that helps a large number of patients
Our press release provides more details on the research and quotes senior author Mark Nicolls, MD, division chief of pulmonary and critical care medicine at Stanford and staff physician at the Veterans Affairs Palo Alto Health Care System:
“Current approved therapies for pulmonary hypertension have focused on dilating blood vessels without special attention being paid to the inflammation that is frequently seen around blood vessels,” Nicolls said. “We were interested in finding out how inflammation contributes to the disease.”
In laboratory experiments, researchers removed inflammation-producing cells called macrophages from the lung tissue of rats dying of pulmonary hypertension and put the cells in cultures with healthy rat endothelial cells.
“We were shocked to find that half of the endothelial cells were dead within 24 hours,” Nicolls said. “That totally surprised us.”
In subsequent lab experiments, researchers found that if they blocked the molecular pathway triggered by the macrophages, the endothelial cells didn’t die. Researchers conducted similar experiments in human tissue taken from the diseased lungs of patients. The results were similar. “The same pathways were at play in the human lungs,” Nicolls said.
In experiments in live rats with induced pulmonary hypertension, the disease was reversed when researchers blocked the inflammation-producing pathway.
“It was dramatic,” Nicolls said. “We could start the drug as late as three weeks when animals were breathing hard and walking slowly, and the disease reversed.”
If further studies show that these results apply to humans as well medications that disrupt this inflamation-producing pathway could provide a new way to reverse, or perhaps cure, pulmonary hypertension. “We believe this is going to be an approach that helps a large number of patients,” said Nicolls.
Holly MacCormick is a writing intern in the medical school’s Office of Communication & Public Affairs. She is a graduate student in ecology and evolutionary biology at University of California-Santa Cruz.
Previously: Racing to raise awareness of pulmonary hypertension, Man receives life-saving transplant thanks to health-care reform and a truck, New arterial insights portend potential treatments for life-threatening diseases and A story from the edge of medical possibility: Operatic soprano sings after double lung transplant