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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月2日

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  • 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

摘要

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.