Pulmonary hypertension is a life-threatening disease marked by an increase in blood pressure in the lungs that makes breathing for patients exceedingly difficult, even while performing a relatively simple task. While there is still much to be learned about this rare and deadly disease, a new study published researchers at Yale School of Medicine on pulmonary hypertension has revealed valuable insights into cells and how they function in relation to the onset and progression of the disease.
The new study, which was published in the February 27th edition of Cell Reports, highlights the researchers’ efforts to learn more about the specific cellular mechanisms that occur behind the scenes in terms of the way that cells are organized in pulmonary arteries in patients who have pulmonary hypertension. It is this organization of cells that has been found to directly lead to patients being short of breath and fatigued, and eventually results in serious outcomes, such as heart failure and death. In order to demonstrate the severity of this cellular disorder, the disease results in a 50% death rate after three years of diagnosis in patients.
Until the publishing of this study, the cellular mechanisms involved in pulmonary hypertension were not well understood. As a result, researchers have had little to go on in terns of how to develop therapies for the disease. However, scientists now believe that if treatments can be developed for pulmonary hypertension that target the abnormal changes in the pulmonary artery structure at the cellular level, that therapies in turn can become increasingly effective.
Daniel Greif, M.D., assistant professor of internal medicine (cardiology), who conducted the study with Yale colleagues Abdul Sheikh and Janet Lighthouse, noted that: “For the first time, we understand which cells are responsible and the cellular processes underlying their recruitment,” and adding that, “We looked at the mechanism involved in how these cells migrate along blood vessels.”
The result of diseases such as pulmonary hypertension and other vascular disorders such as atherosclerosis is the development of excess smooth muscle accumulation in vascular structures in the lungs. Healthy lungs have patterns that are similar is design to that of tree branches, and the smallest blood vessels that branch out from these structures normally do not have a muscular coating. In the case of PH, however,even these small blood vessel branches become muscularized, which in turn leads to labored breathing.
In order to better understand the development of this excess smooth muscle mass in the lungs of patents with pulmonary hypertension, “Greif and colleagues used genetic tools to map the fate of smooth muscle cells in mice with pulmonary hypertension,” according to a recent press release. 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.