• October 2018

CapouladeRomain Capoulade is the French scientific leader of the PICASSO project "Unravelling PCSK9 mechanisms in calcific aortic valve disease: from aortic valve sclerosis to stenosis". This European-funded research project will be carried out by an international consortium of 4 partners (Canada, France, Italy, Germany).

Reinforcing the visibility of l'institut du thorax teams for its work in the field of valvulopathies as well as for its expertise on PCSK9, PICASSO's main goal is to validate PCSK9 as a therapeutic target for the prevention and treatment of patients with calcific aortic valve stenosis (CAVS).
 





Abstract

Calcific aortic valve stenosis (CAVS) is a fatal pathology that affects 2-3% of the population. Yet, drug therapies are ineffective, leaving the urgency to fully characterize the etiology of aortic valve calcification to develop innovative therapies.

Our preliminary data suggest that PCSK9, an important protein for lipid metabolism, plays an active role in CAVS. Therefore, we will determine whether PCSK9 is a causal risk factor for CAVS using genetic epidemiology. Further, we will shed light on the molecular underpinnings through which PCSK9 causes CAVS in humans using state-of-the-art in vivo as well as in vitro models in combination with next-generation sequencing. As a complementary and potential preclinical model, we will determine the role of PCSK9 in the development of aortic valve calcification in mice.

The overarching aim of this research program is to provide the required biological evidence using a highly translational approach to support PCSK9 as a therapeutic target for the prevention and treatment of patients with CAVS.