Efffect of antihypertensive drugs on pulmonary ACE2

Angiotensin converting enzyme 2 (ACE2) is a membrane-bound enzyme which enables the coronavirus (SARS-CoV-2) to gain cellular entry and infect cells. ACE2 can be found in the respiratory tract, the nasal mucosa, the eye, the kidneys, intestine and heart. Next to its role in a SARS-CoV-2 infection, ACE2 also has an important physiological function in that it regulates blood pressure as part of the renin-angiotensin-aldosterone system. This dual function of ACE2 plays a central role in COVID-19. On one hand, a reduction in ACE2 density caused by viral infection may aggravate the severity of the disease. On the other hand, certain patients groups with a high density of ACE2 in different tissues may be at higher risk for viral infection. It has been discussed whether treatment with certain antihypertensive drugs may increase the density of ACE2 in the respiratory tract and thereby increase the risk for viral infection. In this project, we will develop a new positron emission tomography (PET) imaging protocol, which will allow us to measure the density of ACE2 in different body tissues after injection of a small amount of a radioactive compound which binds with high affinity to ACE2. This novel imaging protocol will be used to assess the influence of treatment with antihypertensive drugs on ACE2 density in the respiratory tract. Our imaging protocol will help to better understand the role of ACE2 in SARS-CoV-2 infection and will contribute to the development of new drugs to treat COVID-19.