Cellular and molecular mechanisms of neural control of inflammation and metabolism in cardiovascular disease

Since atherosclerotic plaques lack direct innervation, neural regulation of atherosclerosis was largely disregarded.

We showed, with “Plaquefight consortium” partners, that neuroimmune cardiovascular interfaces control atherosclerosis (Mohanta et al., Nature, 2022), cholinergic neural signals promote inflammation resolution (Caravaca et al., PNAS 2022) and vascular endothelial integrity (Tarnawski et al., PNAS 2023).Based on our previous studies, we hypothesize thatneuroimmune interactions in the adventitia of atherosclerosis-prone artieres regulate atherosclerosis initiation and plaque composition. andautonomic sensory and motor signals promote vascular inflammation and a pro-atherosclerotic phenotype.To investigate this, we propose to use a combination of imaging, sequencing, and novel nerve-blocking/activation-technology in genetic mouse models.

We will define the innervation of the disease-prone arteries, analyze how nerve signals contribute in vascular inflammation and atherosclerosis, and systematically study the effect of specific neural signals on disease onset and development. The project will be based in my research group.

We have established national and international collaborations on data analysis, imaging, neurophysiological technology, and immunometabolism.

Neural regulation of inflammation is already in clinical trials, and we hope that knowledge gained in our program will identify additional potential therapeutic approaches in cardiovascular disease.