Dan Li, Ph.D.
Funded by the American Lung Association of the Upper Midwest
Elucidating Enzyme's Role in Pulmonary Arterial Hypertension
Pulmonary arterial hypertension (PAH) is characterized by elevated blood pressure due to narrowed blood vessels, which result from abnormal growth of pulmonary arterial smooth muscle cells (PASMC). Our preliminary studies indicate that PAH is associated with both abnormal cell metabolism and altered activity of genes that are responsible for the abnormal PASMC growth. We will study an enzyme called ALDH1A3 that is increased in PAH PASMC. We will also use a mouse model that lacks ALDH1A3 to determine the adverse effects of pulmonary hypertension. Our hope is that this project will establish increased ALDH1A3 in PASMC as a potentially promising target for PAH therapy.
Update: In order to better understand the metabolic and genomic changes that take place in PASMC in patients with PAH, we looked for candidate genes that play important roles in cell metabolism and cell proliferation related to disease progression. Comparing PASMC from healthy donors and PAH patient lungs, we found 87 significantly changed genes. These genes draw a "disease map" that can help trace cell signaling pathways that may cause abnormal PASMC to drive PAH. Among them we found ALDH1A3 is responsible for the abnormal cell growth of PAH PASMC. We are using a mouse model in which this key gene is depleted to verify our hypotheses. Our findings will bring novel insights and therapeutic strategies to PAH.