The primary function of the lungs is to oxygenate blood—a process that relies on several carefully coordinated mechanisms. Air travels through the airways to tiny air sacs called alveoli, where gas exchange occurs. Deoxygenated blood from the heart reaches the alveoli via the pulmonary arteries, and after picking up oxygen, it returns to the heart through the pulmonary veins for circulation throughout the body. The pulmonary arteries and veins—together known as the pulmonary vessels—play a key role in this process. Dysfunction in these vessels can result in serious, sometimes life-threatening, health complications.
Pulmonary arterial hypertension (PAH) is a progressive disease that impairs the function of pulmonary vessels. It is characterized by the abnormal growth of smooth muscle cells within the pulmonary arteries, leading to narrowing and eventual obstruction of the vessels. This results in elevated pressure in the lung circulation, forcing the heart to work harder and potentially leading to right heart failure. Despite recent advancements in treatment, PAH remains a life-threatening disease with no definitive cure. Current therapies—such as sotatercept, ambrisentan, tadalafil, and treprostinil—can reduce the disease burden in some patients. However, the development of more effective and curative treatments remains a central goal in PAH research.
PAH is significantly more common in women than in men; for every man with PAH, there are approximately two to four women affected. The reasons for this sex difference are not yet fully understood. One possible explanation is that female hormones, such as estrogen, may increase the likelihood of blood vessel narrowing or damage, which can contribute to PAH. Studies also suggest that differences in the immune response—particularly how women respond to inflammation and injury—may play a role. In addition, recent research indicates that sex chromosomes may be involved in this process; however, the underlying mechanisms remain poorly understood.
The greatest challenges in our laboratory were:
1. distinguishing between male and female PAH patients,
2. identifying the causes of PAH development in both sexes, and
3. developing precision medicine and targeted treatments for male and female PAH patients.
The completion of this project will also influence future research directions in the field of PAH, as it opens the possibility of treating male and female patients by selectively targeting the lung vasculature. Furthermore, the knowledge gained may contribute to the development of treatments for other pulmonary diseases, such as acute respiratory distress syndrome (ARDS).
