$11.5 million award renewal from NIH supports study of how stress influences cardiovascular health

Psychosocial stress profoundly affects people's lives globally, not least because it can be a critical risk factor for cardiovascular disease. Thanks to an $11.5 million award renewal from the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health, distinguished researchers at the Icahn School of Medicine at Mount Sinai and elsewhere aim to gain a deeper understanding of how stress influences cardiovascular health.

To address residual cardiovascular risk in patients, our research program aims to bolster our mechanistic understanding of how psychosocial stress impacts the immune system and inflammatory atherosclerosis. We are delighted that NHLBI has validated the potential of our work by enabling this program through the renewal of this grant."

Zahi Fayad, PhD, Principal Investigator, Director of the Biomedical Engineering and Imaging Institute and Lucy G. Moses Professor in Medical Imaging and Bioengineering at Icahn Mount Sinai

Existing cardiovascular risk management strategies lack sufficient evidence-based interventions to tackle the adverse effects of psychological stress. Given the escalating burden of atherosclerotic heart disease, the investigators emphasize the urgent need to modulate the impact of stress.

Dr. Fayad reported on developments to come out of the initial five-year grant: "We significantly advanced knowledge on psychosocial stress and cardiovascular disease by identifying connections between the nervous, immune, and vascular systems. Our findings showed that stress perception mechanisms influence atherosclerosis development and regression. And we developed sophisticated tools to study brain regions involved in stress perception and made substantial progress in translational imaging studies to measure stress-associated neurobiology as it relates to cardiovascular disease. Additionally, our clinical studies are shedding light on the neuro-immune-arterial pathway. Collaboratively, we have generated innovative research questions we're now eager to explore."

Dr. Fayad will lead a multidisciplinary team from Icahn Mount Sinai, Massachusetts General Hospital (MGH), New York University (NYU), and Radboud University Medical Center (Radboudumc)

in the Netherlands to complete the interrelated experiments. The team includes Filip Swirski, PhD, Scott Russo, PhD, Philip Robson, PhD, Li Shen, PhD, Abraham Teunissen, PhD, MSc, BASc, Maria Giovanna Trivieri, MD, PhD, and Mandy van Leent, MD, PhD, from Icahn Mount Sinai; Willem Mulder, PhD, and Niels Riksen, MD, from Radboudumc; Edward Fisher, MD, PhD, MPH, from NYU; and Ahmed Tawakol, MD, Matthias Nahrendorf, MD, PhD, and Lisa Shin, PhD, from MGH.

Building on the previous five-year grant, the research team plans to broaden their perspective to better understand immune reprogramming in psychosocial stress-aggravated atherosclerotic disease. The work will involve:

• Evaluating various brain circuits
• Utilizing diverse imaging methods
• Conducting in-depth analyses (omics) for optimal integration and harmonization of data

"This research has the potential to not only advance our scientific understanding of neural control of immune mechanisms that drive cardiovascular diseases, but also could offer approaches to managing such diseases in individuals experiencing prolonged psychosocial stress, including identifying novel therapeutic targets, treatments and preventive measures," says Eric J. Nestler, MD, PhD, Nash Family Professor of Neuroscience, Director of The Friedman Brain Institute, and Dean for Academic Affairs at Icahn Mount Sinai, and Chief Scientific Officer of the Mount Sinai Health System.

The work is being supported by the National Heart, Lung, and Blood Institute (grant number P01HL131478).