100 Section - Pulsed electromagnetic fields inhibit atherosclerosis by regulating pyroptosis through membrane tension-mediated mechanosensitive channels

Atherosclerosis serves as the core pathological basis of cardiovascular, cerebrovascular, and peripheral arterial diseases, posing a serious threat to human health. However, current mainstream treatments such as statin drugs and stent implantation are associated with significant side effects or limited efficacy, highlighting the urgent need for new therapeutic strategies. Pulsed electromagnetic fields (PEMFs), due to their noninvasive nature and anti-inflammatory properties, show potential in the treatment of atherosclerosis.

Design:

We used ApoE-/-mice, ApoE-/-NLRP3-/-mice, human umbilical vein endothelial cells, and human plasma to jointly carry out experimental verification from three dimensions. We have used conventional molecular biology methods and cell biology methods, as well as new experimental methods such as proteomics and fluorescence lifetime technology, in an effort to provide complete evidence for studying the role of PEMFs in atherosclerosis and its potential mechanisms.

Results:

The study revealed significant endothelial cell (EC) inflammation and pyroptosis during the progression of atherosclerosis. PEMFs were found to effectively inhibit the activation of the NLRP3 inflammasome, reduce plaque formation, and delay the progression of atherosclerosis. Proteomic analysis of plasma from atherosclerosis patients further indicated elevated expression levels of proteins related to inflammation and pyroptosis, with particularly notable changes in membrane proteins. Mechanistic studies demonstrated that PEMFs improve mitochondrial dysfunction in ECs by regulating membrane tension and the mechanosensitive tension-mediated transient receptor potential vanilloid 4 (TRPV4) channels, thereby reducing pyroptosis.

Conclusion:

This discovery not only reveals a novel mechanobiological pathway but also provides a solid theoretical foundation for the development of PEMF-based therapies for atherosclerosis.