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Yale study provides a breath of hope for pulmonary hypertension patients

Yale study provides a breath of hope for pulmonary hypertension patients
2014-02-27
(Press-News.org) Most of us draw roughly 25,000 breaths a day without any thought. But for patients with pulmonary hypertension, a life-threatening increase in blood pressure in the lungs, even the smallest task can leave them gasping for air. A new study by researchers at Yale School of Medicine offers insight into the function of cells linked to this incurable and often fatal illness.

Published Feb. 27 in Cell Reports, the study is the first to explore the cellular mechanisms behind the changes in the way cells are organized in pulmonary arteries in pulmonary hypertension, which leaves patients short of breath and fatigued, and ultimately results in heart failure and death. Almost half of patients die within three years of diagnosis.

Up until now, these mechanisms were not well understood, leaving clinicians with little guidance on how to prevent or reverse them. Scientists believe the fate of these patients could be improved if treatments were designed to address the abnormal changes in the pulmonary artery structure.

"For the first time, we understand which cells are responsible and the cellular processes underlying their recruitment," said senior author Daniel Greif, M.D., assistant professor of internal medicine (cardiology), who conducted the study with Yale colleagues Abdul Sheikh and Janet Lighthouse. "We looked at the mechanism involved in how these cells migrate along blood vessels."

Excess smooth muscle accumulation is a key component of pulmonary hypertension and other vascular disorders such as atherosclerosis. Vascular structures in the lung have patterns reminiscent of tree branches, and the smallest blood vessels normally lack a muscular coating; however, in pulmonary hypertension they become muscularized.

Greif and colleagues used genetic tools to map the fate of smooth muscle cells in mice with pulmonary hypertension. They focused on specific small vessels and determined that the smooth muscle coating comes from smooth muscle cells of larger vessels. "We also discovered the process by which smooth muscle cells differentiate, migrate to small blood vessels, and then re-differentiate, thereby muscularizing vessels that normally lack a smooth muscle cell coating," said Greif.

"Now that the culprit cell population in pulmonary hypertension is identified, we can turn our attention to tailoring therapies to target these cell," he added.

INFORMATION: The study was funded in part by a Senior Research Fellowship from the American Lung Association; the National Institute of Health under the Ruth L. Kirschstein NRSA Institutional Training Grant (2T32HL007950); the March of Dimes (Basil O'Connor Award, 5-FY13-208); the Pulmonary Hypertension Association (Clinical Scientist Development Award); and National Institute of Health (5K08HL093362, and CTSA 5UL1RR024139-08 through the National Center for Advancing Translational Science (NCATS).

Citation: Cell Reports doi: 10.1016/j.celrep.2014.01.042 (Feb. 27, 2014)

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Yale study provides a breath of hope for pulmonary hypertension patients

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[Press-News.org] Yale study provides a breath of hope for pulmonary hypertension patients