12,13-diHOME protects against the age-related decline in cardiovascular function via attenuation of CaMKII

12,13-diHOME protects against the age-related decline in cardiovascular function via attenuation of CaMKII

Abstract Aging poses significant challenges to cardiovascular health necessitating novel therapeutic approaches. This study investigates the potential of the brown adipose tissue (BAT) derived lipokine 12,13-diHOME to mitigate age-induced impairments in cardiovascular function. Analysis of human and...

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Main Authors: Shinsuke Nirengi, Benjamin Buck, Devleena Das, Carmem Peres Valgas da Silva, Jazmin Calyeca, Lisa A. Baer, Hsiang-Ling Huang, Pablo Vidal, Revati S. Dewal, Kelsey M. Pinckard, Elisa Félix-Soriano, Diego Hernandez-Saavedra, Andrew Gerea, Kavya Dathathreya, Silvia Duarte-Sanmiguel, Ty A. Saldana, Harrison L. Hookfin, Matthew W. Gorr, Valerie Bussberg, Juan J. Aristizabal-Henao, Michael A. Kiebish, Roeland J. W. Middelbeek, Laurie J. Goodyear, Paul M. Coen, Krishna Chinthalapudi, Loren E. Wold, Ana L. Mora, Thomas J. Hund, Daniel Gallego-Perez, Kristin I. Stanford
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-62474-7
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Summary:Abstract Aging poses significant challenges to cardiovascular health necessitating novel therapeutic approaches. This study investigates the potential of the brown adipose tissue (BAT) derived lipokine 12,13-diHOME to mitigate age-induced impairments in cardiovascular function. Analysis of human and rodent plasma signaling lipids reveals a decline in 12,13-diHOME levels with age. Transplantation of BAT or sustained upregulation of 12,13-diHOME effectively preserved cardiac function in aged male and female mice. Bulk RNA-Seq of hearts from aged mice reveals significant increases in pathways involved in ER stress and fibrosis which were partially attenuated by BAT transplantation or sustained upregulation of 12,13-diHOME. Mechanistically, in vivo and in vitro models demonstrate that 12,13-diHOME alleviated ER stress through CaMKII inhibition, particularly in males. These findings underscore 12,13-diHOME as a promising candidate for combating age-related cardiovascular dysfunction, offering insights into potential therapeutic strategies for addressing cardiovascular diseases in aging populations.
ISSN:2041-1723

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