Speaker: Dr Sarajo Mohanta

Title: Neuroimmune Cardiovascular Interfaces in Atherosclerosis

Abstract: 

Atherosclerosis is a chronic inflammatory disease of arteries caused by plaques in the inner layer of arteries. As plaques lack nerve fibers, the impact of neuronal control on atherosclerosis has not been considered before. Since the nervous system uses the adventitia, i.e. the outer connective tissue coat of arteries, as their major conduit to reach distant targets, we hypothesized that the nervous system may interact with diseased arteries via adventitial immune cells to sense and affect atherosclerosis. We identified and functionally delineated tripartite interactions between nerves, immune cells and diseased arteries in murine and human atherosclerosis using tissue clearing, multiplex immunostaining, intact aorta imaging, virus tracing, and single cell transcriptomics. We observed that atherosclerotic adventitia segments interact with the nervous system by stimulating axon growth adjacent to atherosclerotic plaques. Peripheral axon terminals directly interact with immune cells and form neuroimmune junctions. These interactions initiate a structural artery-brain circuit that directly wire diseased arteries with the brain to sense and affect atherosclerosis via dorsal root ganglia, sympathetic ganglia and the spinal cord. Multiplex imaging and electrophysiological nerve recordings revealed activation of central and peripheral components of artery-brain circuits in parallel to disease progression. When these interactions are disrupted by systemic or local sympathetic denervation in mice, plaque-associated immune cell aggregates in the adventitia destabilized, plaques shrunk and showed a more stable phenotype. These data provide a new disease paradigm to understand atherogenesis through multisystemic tissue interactions between the nervous system, the immune system and the cardiovascular system. In summary, our data demonstrated that neuroimmune cardiovascular interactions affect atherosclerosis progression. These studies suggest that neuroimmune cardiovascular interfaces represent new targets using pharmaceutical, surgical and bioelectronic modulations before the disease including becomes life-threatening.

Bio:

Dr. Mohanta studied veterinary medicine in India followed by a master in biomedicine degree at University of Portsmouth in the United Kingdom. He completed his PhD training on vascular biology at the Institute for Vascular Medicine at the Friedrich-Schiller-University Jena under the supervision of Prof. Andreas Habenicht. After graduation, he joined the Institute for Cardiovascular Prevention (Director: Prof. Christian Weber) at the Ludwig-Maximilians-University (LMU) Munich as a postdoctoral research fellow with a special interest in vascular biology and atherosclerosis. Dr. Mohanta is currently an independent group leader at the LMU Munich. His studies focus on the complex mechanisms of interactions between vascular cells, immune cells and neurons underlying cardiovascular diseases and ageing with the support of multiple national and international third-party funding. His group recently demonstrated a functional role of neuroimmune cardiovascular interfaces that act as key pathogenic principles of atherosclerosis development (Nature 2022). He also contributed to define altered neurovascular interactions in the heart during ageing using denervation methods (Science 2023) and to identify T cell tolerance breakdown in atherosclerosis using single cell T cell receptor sequencing (Nat Cardiovasc Res 2023). He was appointed as co-speaker of the German Centre for Cardiovascular Research innovation cluster on heart and brain interfaces in 2023.