Mechanistic Study of Platelet Membrane-Coated Resveratrol Nanosystem in Mitochondrial Dysfunction and Endothelial Senescence During Atherosclerotic Lesion Development via FOXM1 Activation.

Authors

Li Xiao, Zexin Zhan, Ping Liu, Bing Qin

Published in

Aging cell. Volume 25. Issue 8. Pages e70632.

Abstract

Atherosclerosis (AS) is closely linked to endothelial cell (EC) senescence and mitochondrial dysfunction, which impair vascular repair. Resveratrol (RSV) has antioxidant, anti-inflammatory, and pro-angiogenic effects, but its clinical use is restricted by poor bioavailability. This study aimed to construct a platelet membrane-coated resveratrol nanosystem (PM@RSV NPs) and investigate its mechanism of action in delaying the progression of AS by activating FOXM1 to improve mitochondrial function, inhibit EC senescence, and promote vascular regeneration. PM@RSV NPs were prepared using a solvent evaporation method combined with membrane-coating technology, and gene expression profiles and key regulatory networks were analyzed through RNA sequencing (RNA-seq), gene set enrichment analysis (GSEA), and least absolute shrinkage and selection operator (LASSO) regression. In vitro, PM@RSV NPs enhanced mitochondrial membrane potential and ATP generation while decreasing ROS accumulation and the number of SA-β-Gal-positive cells, accompanied by FOXM1 upregulation in ECs. In vivo experiments demonstrated that PM@RSV NPs significantly reduced plaque area, improved mitochondrial function, decreased levels of senescence markers, and promoted vascular regeneration via FOXM1 regulation. In addition, PM@RSV NPs preferentially accumulated in ox-LDL-injured MAECs and AS lesion-associated vascular endothelium, mainly through platelet-membrane adhesion proteins such as GPV and P-selectin; their biosafety was evaluated by EC viability/apoptosis assays, histological examination of major organs, and serum biochemical indices of liver and kidney function. This study confirmed that PM@RSV NPs improved mitochondrial function, inhibited endothelial senescence, and enhanced vascular regeneration by activating FOXM1, offering a novel therapeutic strategy for treating AS.

PMID:
42479952
Bibliographic data and abstract were imported from PubMed on 22 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.