Project: Exploring the effects of microcalcification on plaque vulnerability

Acronym	MICROEXPLORATION (Reference Number: 1. JTC-2017_23)
Project Topic	Cardiovascular calcification has emerged as a predictor of and contributor to cardiovascular morbidity and mortality. Plaque ossification, also referred to as macrocalcification, appears to stabilize plaques. On the other hand, histopathological evidence suggests that subcellular microcalcifications, which form earlier in the thin collagen-based fibrous cap, reduce plaque integrity and trigger rupture and subsequent acute cardiovascular events. However, the direct proof of this detrimental effect and the in vivo role of microcalcification on plaque vulnerability have never been addressed. We aim to determine the effects of microcalcification inhibition on plaque inflammation and remodeling, using a recently developed and characterized inhibitor of tissue-nonspecific alkaline phosphatase (TNAP). Upon prevention of microcalcification in atherosclerotic mice, we will longitudinally analyze inflammation and plaque evolution with μMRI, histology and 18F-NaF PET. Moreover, we aim to identify the molecular mechanism responsible for microcalcification, with particular focus on TNAP activation. Collectively, this project will provide the first data on the effects of microcalcification on plaque evolution. This research program might generate novel therapeutic and diagnostic strategies to control pathophysiological calcification response that is of high unmet clinical need.
Network	ERA-CVD
Call	Joint Transnational Call for Proposals 2017: Mechanisms of early atherosclerosis and/or plaque instability in Coronary Artery Disease

Project partner

Number	Name	Role	Country
1	University of Lyon	Coordinator	France
2	RWTH University	Partner	Germany
3	Nencki Institute of Experimental Biology, Polish Academy of Sciences	Partner	Poland