Inflammation of the arteries is one of the main precursors and drivers of cardiovascular disease, the leading cause of death in the United States. This inflammation is associated with the buildup of dangerous plaque inside the arteries. Advanced treatments are needed to target this inflammation in patients. Researchers at Michigan State University have tested a new infusion of nanotherapeutic nanoparticles that precisely targets inflammation and activates the immune system to help clear arterial plaque.
The research is published in the journal Natural communications.
“There are two different things that people seem to be afraid of when it comes to plaques,” said Bryan Smith, an associate professor in the College of Engineering’s department of biomedical engineering and the Institute of Science and Technology. Quantitative Health Engineering from MSU. “A lot of people don’t really understand the difference between them.”
The first example is when your artery becomes blocked (for example, a 95-99% blockage). Often, symptoms such as chest pain or pressure or nausea and dizziness appear beforehand and doctors place a stent in the artery to increase blood flow. The second is when the plaque is very inflammatory. This can make the plaque vulnerable to rupture, which can lead to blocked arteries elsewhere in the body.
“It’s the scariest problem that leads to most heart attacks,” Smith said. “Because such plaques do not necessarily block a large part of the artery, and because the effects of the rupture can very suddenly completely block blood flow, such a heart attack can seem to come out of nowhere.”
Smith and his team, including postdoctoral co-authors Yapei Zhang and Manisha Kumari, created nanoparticles (materials finer than a human hair) that they used to develop a nanotherapy infusion. Nanotherapy selectively targets a specific type of immune cell that enters and becomes part of the plaque. These treated cells “eat away” at parts of the plaque core, removing it from the artery wall and decreasing levels of inflammation in the blood vessels.
Previous studies by Smith and colleagues, the Leeper Lab at Stanford University, tested the perfusion in mice and now in porcine models, to prove the efficacy of the perfusion and, more importantly, its lack of harm. side effects due to its precise immune targeting.
“Using PET (positron emission tomography), we were able to measure the effects of the therapy on the pigs’ arteries,” Smith said. “We have shown in animal models such as pigs that we can decrease levels of inflammation in plaque, not only through this PET imaging technique used clinically, but also through molecular testing. Equally important , we did not see any of the side effects that would have been anticipated if the therapy had not been precisely targeted.”
Previous studies in mice required hundreds of microliters of nanotherapy infusion, but more recently, Smith and his team achieved a measurable impact in pigs by increasing the amount produced in liters. These volumes are within the range necessary for human use. This study represents a crucial step toward translating safer and more effective cardiovascular therapies into patient clinical trials.
More information:
Sharika Bamezai et al, Pro-efferocyte nanotherapies reduce vascular inflammation without inducing anemia in a large animal model of atherosclerosis, Natural communications(2024). DOI: 10.1038/s41467-024-52005-1
Provided by Michigan State University
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