Document Type
Article
Publication Date
3-18-2025
Original Citation
Zong P,
Li C,
Feng J,
Yue Z,
Legere N,
Yu A,
Shah F,
Perez A,
Li Z,
Jellison E,
Mori Y,
Miller B,
Verma R,
Liang B,
Yue L.
TRPM2 overactivation drives hyperlipidemia-induced dysfunction of myeloid cells and neurovascular units. Cell Rep Med. 2025;6(3):101998.
Keywords
JGM, TRPM Cation Channels, Animals, Hyperlipidemias, Humans, Myeloid Cells, Mice, Male, Mice, Inbred C57BL, Mice, Knockout, Disease Models, Animal, Brain Ischemia
JAX Source
Cell Rep Med. 2025;6(3):101998.
ISSN
2666-3791
PMID
40056905
DOI
https://doi.org/10.1016/j.xcrm.2025.101998
Abstract
Hyperlipidemia induces cellular dysfunction and is strongly linked to various diseases. The transient receptor potential channel melastatin 2 (TRPM2) plays a critical role in endothelial injury, immune cell activation, and neuronal death. We reveal that TRPM2 expression in human peripheral leukocytes strongly correlates with plasma lipid levels. In middle-aged Apoe/ mice, global, myeloid, and endothelial TRPM2 knockout or TRPM2 inhibition abolishes the hyperlipidemia-induced exacerbation of ischemic brain injury suggesting that TRPM2 overactivity caused by hyperlipidemia predisposes these cells to dysfunction during ischemia. Using a clinically relevant ischemic brain injury mouse model, we demonstrate TRPM2’s pivotal role in medi- ating hyperlipidemia’s detrimental effects on myeloid cells and neurovascular units. Our findings suggest that TRPM2 is a promising therapeutic target for alleviating neurodegenerative diseases exacerbated by hyper- lipidemia, such as ischemic stroke. These results also highlight TRPM2 expression in peripheral blood as a potential biomarker for predicting stroke outcomes in hyperlipidemic patients.
Comments
This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).