Insights into the renin-angiotensin system in ATTR-CM

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a condition that can lead to the deposition of proteins in organs due to genetic or age-related changes in the structure of the transthyretin protein. Often, these so-called "amyloid fibrils" can also accumulate in the heart, leading to significant stiffness and functional impairment of heart function, which in turn results in progressive heart failure. The renin angiotensin-system (RAS) is crucial for maintaining fluid and salt balance and plays a significant role in regulating blood pressure and the progression of heart failure. Some proteins involved in regulating the RAS have negative effects on the cardiovascular system, while others may have positive effects and the balance between them seems to be essential for maintaining heart and kidney health. Medications used to treat other forms of heart failure, which have repeatedly shown good results, primarily act on the renin-angiotensin system (RAS) by inhibiting its negative effects on the cardio- vasculature. Unfortunately, these medications have not proven to be beneficial in patients with ATTR-CM and in some cases may even worsen symptoms. However, it is not known why these therapies are ineffective in ATTR-CM. The goal of our research is to characterize the disease by analyzing the quantity and ratio of RAS proteins measured from blood samples of patients with previously diagnosed ATTR-CM. This could help us better understand the diseases development. Additionally, we aim to investigate how the levels of these proteins correlate with symptoms and changes in heart structure, and whether they can predict which patients may experience a more rapid the disease progression.