Project: Fighting Atherosclerotic Plaques in Coronary Artery Disease Via Targeting Neuroimmune Interfaces

Acronym	PLAQUEFIGHT (Reference Number: 8. JTC-2017_62)
Project Topic	Atherosclerosis is caused by plaques in the inner layer of arteries. Plaque instability triggers clinically significant disease including coronary artery disease (CAD). However, there is currently no causal therapeutic approach to treat CAD and the pathophysiological mechanisms of atherosclerosis largely remain to be uncovered. We focused on possible interactions between atherosclerosis-associated adventitia inflammation and the nervous system (NS), a research area previously unexplored as atherosclerotic plaques are not innervated. Our preliminary studies showed that atherosclerosis initiates immune-neurovascular interactions with the peripheral NS (PNS) in Apolipoprotein E-deficient (ApoE-/-) mice via atherosclerosis-associated adventitia innervation. We found that artery tertiary lymphoid organs (ATLOs) and fat-associated lymphoid clusters (FALCs) in the adventitia of arteries interact with the PNS, by stimulating axon growth and infiltrating paraaortic ganglia, dorsal root ganglia, and nerves. We also identified a putative atherosclerosis-brain-circuit (ABC) connecting the adventitia/ATLOs and distinct brain nuclei using retroviral, i.e. pseudorabies virus (PrV), tracing technologies. Thus, immune-neurovascular interactions form ABCs that sense, respond to, and may affect atherosclerosis. To study the functional impact of ABCs, we plan to i) ablate components of the PNS; ii) study the morphopathology of ABCs; iii) determine whether PNS conductance is altered in atherosclerosis; and iv) validate our results in human cardiovascular tissues in translational approaches.
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	Ludwig-Maximilians-University Munich	Coordinator	Germany
2	IRCCS Neuromed	Partner	Italy
3	Institut National de la Santé et de la Recherche Médicale (INSERM)	Partner	France
4	Jagiellonian University	Partner	Poland