Eliminate cholesterol crystals with a new nanoparticle

An innovative nanoparticle could one day help fight an incurable risk factor for heart attacks and strokes: cholesterol crystals that trigger inflammation and escape drugs.

“Although lipid-lowering drugs significantly prevent cardiovascular events in atherosclerosis, some patients still suffer from a high residual risk because the cholesterol crystals existing in the atherosclerotic plaques activate immune cells and trigger inflammatory responses, ”said Y. Eugene Chen, MD, Ph.D., professor of internal medicine, cardiac surgery, physiology, pharmacology and medicinal chemistry, University of Michigan Frankel Cardiovascular Health Center, who was the lead author of a new publication on the nanoparticle. “We presented a new therapeutic strategy for atherosclerosis by modulate components in plaques and counteract inflammation induced by cholesterol crystals.

The nanoparticle generated by Chen’s team, known as miNANO, for the Michigan nanoparticle, removed crystals from hardened arteries in mouse models of atherosclerosis, thereby making aortic plaques more stable. With a diameter of only 10nm, much smaller than what is visible to the human eye, miNANO is phospholipid-based and behaves like HDL cholesterol, known as good cholesterol, which cleanses the arteries and prevents additional hardening. When the nanoparticle performed well in mouse models, the team then tested it in human aortic tissue with similar results.

Co-lead author Anna Schwendeman, Ph.D., William I. Higuchi Collegiate Professor of Pharmacy, has extensive experience in the discovery and clinical development of synthetic high-density lipoprotein nanomedicines. She stated that this newly generated nanoparticle exhibits strong biological function as a cholesterol acceptor and cholesterol crystal dissolving agent, with a significantly longer circulation half-life compared to synthetic HDL cholesterol.

Cholesterol crystals were first discovered in atherosclerotic plaques in the early 1900s and have been identified in many other diseases, including Niemann-Pick lysosomal overload disease type C, aneurysm of abdominal aorta, kidney disease, and central nervous system abnormalities, the authors said.

“Our studies not only suggest an effective pharmacological target for reducing atherosclerotic plaque load, but also provide a novel strategy to treat other diseases,” said co-lead author Yanhong Guo, MD, Ph.D., professor. internal medicine assistant at UM Health Frankel Cardiovascular Center.

The research team has been collaborating for more than seven years on targeted therapy of cardiovascular disease using nanoparticles and drug delivery to atheroma through nanoparticles.

The human aortic tissue tested in this study was made available through UM Health cardiac surgery patients who volunteered to participate in the research.

The results do not necessarily represent the position of the National Institutes of Health (HL134569, HL109916, HL136231, HL137214, HL138139, R21NS111191 and T32 GM07767), which funded work with the American Heart Association, the Aikens Aortic Discovery grant from the UM Health Frankel CVC, pilot grant from the UM Biointerfaces Institute and the Barbour grant from the UM.

Cited article: “Phospholipid nanoparticles: therapeutic potentials against atherosclerosis by reducing cholesterol crystals and inhibiting inflammation.” ” EBioMedicine a review published by The Lancet, DOI: 10.1016 / j.ebiom.2021.103725

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