New treatments for right ventricle in pulmonary arterial hypertension (PAH)

The aim of this project is to determine the difference between males and females in the mitochondrial function (the mitochondria are the energy engines of the cell) of the right side of the heart with the aim of identifying new ways to treat pulmonary arterial hypertension. Pulmonary arterial hypertension (PAH) is a disease that causes high blood pressure in the arteries that go from the right side of the heart to the lungs. PAH is a rapidly progressive disease resulting in right heart failure and death. The 5-year survival is 37%, and over 15,000 deaths per year are ascribed to PAH.

Though right heart function mainly determines the clinical outcome of patients with PAH, no effective therapy directly treats the right heart in PAH. It is also known that there is sex difference in PAH: 3-4 times more women than men develop this disease, however, women have better right heart function and thus their survival rates are better than men. Right heart failure is also related to mitochondrial dysfunction. Mitochondria, the powerhouse of the cell, is an important cellular component that not only produces about 90% of energy that cells need to survive but also regulates other cellular functions. Currently, the effect of sex hormones on the mitochondrial function in the right heart in PAH is not well studied. Since the availability of right heart tissues from human PAH patients is limited, this research program will instead make extensive use of a well recognized and often used method of studying PAH in rats. The adult rats will be used to mimic the effects of PAH so that it can be studied. This project will study the sex difference in the mitochondrial function in the right heart in the animal model and identify novel potential therapeutic targets for the right heart in PAH.

As a result of this research, it is hoped that the sex-dependent mitochondrial function in the right heart in the animal model of PAH will be well determined and that possible new treatments for the right heart in PAH will be proposed for further clinical trials. Information from this research will be shared via published papers and will give other scientists in the field a clearer understanding of the role of mitochondria. We will present our new data or findings in seminars and national and international conferences, and publish the new knowledge in scientific journals. We will also collaborate with clinicians and scientists to develop clinical trials if potential therapeutic targets are identified. In the longer term, patients will benefit through novel therapies becoming available if full clinical trials are successful.