Project: Unravelling proprotein convertase subtilisin/kexin type 9 (PCSK9) mechanisms in calcific aortic valve disease: from aortic valve sclerosis to stenosis

Acronym	PICASSO
Duration	01/05/2019 - 30/04/2021
Project Topic	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.
Network	ERA-CVD
Call	Joint Transnational Call for Proposal 2018 (JTC 2018)

Number	Name	Role	Country
1	Centro Cardiologico Monzino IRCCS	Coordinator	Italy
2	University of Bonn	Partner	Germany
3	Laval University	Partner	Canada
4	INSERM – Nantes University	Partner	France