Pulmonary Hypertension

Pulmonary hypertension (PH) is a devastating disease that affects people at all ages, including young women of childbearing age. Although medical therapies have vastly improved, many PH patients eventually require lung transplantation. Therefore, understanding the pathophysiological mechanisms of PH is critical. The laboratory is currently focused on two aspects of PH pathophysiology that may help identify novel therapeutic avenues for this disease. These include:

Hypoxia and neurotrophins

Hypoxia is well-known as a risk factor for PH. Recent evidence suggests that neurotrophins and their receptors are expressed in the pulmonary artery. Results from the laboratory show that brain-derived neurotrophic factor (BDNF) regulates endothelial nitric oxide synthase (eNOS) and thus modulates pulmonary vasodilation. However, BDNF can worsen vascular smooth muscle contraction and vascular remodeling. Furthermore, hypoxia modulates BDNF and conversely, BDNF worsens hypoxia effects. Studies in the lab are now exploring how these interactions occur in order to test the possibility of interfering with BDNF to blunt PH.

Estrogens

PH in young women is a particular problem. Estrogens are thought to play a role, yet it is paradoxical that the same estrogens that are thought to be protective in coronary artery disease are detrimental in PH. Using arterial samples from male versus female patients, both with and without PH, and in animal models of PH, researchers are exploring new areas. The novel idea is that local tissue aromatases, rather than circulating estrogens, are key determinants of estrogen effects in PH.