Cardiovascular Disease (CVD) is a set of multifactorial pathologies that cause over 30% of the annual deaths worldwide and they are the most frequent cause of death in the European Union. Exploring the vast complexity of the biological mechanisms and patient-dependent factors in CVD represents a challenge that requires joint multidisciplinary efforts to be tackled successfully. The present project aims to obtain novel knowledge at the molecular level of Reverse Cholesterol Transport (RCT), one of the key hallmarks for CVD. Our results will ultimately guide the design and development of improved and more specific therapeutic approaches to CVD. Becoming an IMIBIC-P2Med fellow will have a decisive impact in my career since I will get the full support of the institution to develop critical skills, such as mentoring, leadership and management, through focused training and teaching activities.

The objective of the HIDELIS project is to study the structural features and dynamics guiding the paraoxonase 1 (PON1) activity, a key antioxidant marker, and the serum amyloid A (SAA) activity, and anti-inflammatory marker, in the context of the HDL particle. To obtain a comprehensive view of their mechanisms of action in a native-like environment, I will explore the interaction of these proteins with the lipidic bilayer, and its relevance to apolipoproteinA-I, the main scaffold protein in HDL.

With this integrative view, I aim to obtain novel information of the structure-function relationship of these key proteins in HDL that will allow us to rationalize the molecular basis for their activity and their impact in the loss of HDL functionality. This new knowledge will allow us to devise new therapeutic approaches to modulate these essential activities in dysfunctional HDL in the context of CVD and atherosclerosis.