Research Project: Role of Protective Factor in Right Heart Failure
Pulmonary hypertension (PH) is a disease characterized by narrowing of the blood vessels of the lung; leading to high blood pressure in the lungs, right heart failure and death. Survival is determined by right heart function. Patients with poor right heart function are more likely to succumb to disease and patients with preserved right heart function are more likely to survive. Our study addresses how the protective factor apelin regulates the right heart, and whether apelin-mediated signaling could be developed as a new therapy. Specifically, we want to identify how apelin regulates cells in the heart and if inhibiting apelin worsens heart function. Once we complete our studies, we will have identified what changes as the heart fails and established new ways apelin stops right heart failure. Our studies will lead to the development of new therapies for PH patients.
We found a new way apelin signals from heart cells to cells of the blood vessels. We can use this finding as a test to identify how apelin changes signaling in unhealthy cells from failing right hearts. We also found that apelin can restore normal cell function in unhealthy blood vessel cells from failing hearts, suggesting it could potentially be used as a therapy in patients with poor right heart function. Finally, we found that rodents without apelin signaling had more severe right heart failure and decreased survival, supporting our hypothesis. Our next steps are to use a new technique called single cell RNA-Seq to identify specifically what changes in hearts without apelin signaling and to determine if these changes are the same between males and females. Once we complete our studies, we will have identified what changes as the heart fails and established new ways apelin stops right heart failure. Our studies will lead to the development of new therapies for PH patients.