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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62474-7 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Shinsuke Nirengi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e914fa343a7c48d2affdd61a9017c914 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e914fa343a7c48d2affdd61a9017c9142025-08-20T04:03:03ZengNature PortfolioNature Communications2041-17232025-08-0116111510.1038/s41467-025-62474-712,13-diHOME protects against the age-related decline in cardiovascular function via attenuation of CaMKIIShinsuke Nirengi0Benjamin Buck1Devleena Das2Carmem Peres Valgas da Silva3Jazmin Calyeca4Lisa A. Baer5Hsiang-Ling Huang6Pablo Vidal7Revati S. Dewal8Kelsey M. Pinckard9Elisa Félix-Soriano10Diego Hernandez-Saavedra11Andrew Gerea12Kavya Dathathreya13Silvia Duarte-Sanmiguel14Ty A. Saldana15Harrison L. Hookfin16Matthew W. Gorr17Valerie Bussberg18Juan J. Aristizabal-Henao19Michael A. Kiebish20Roeland J. W. Middelbeek21Laurie J. Goodyear22Paul M. Coen23Krishna Chinthalapudi24Loren E. Wold25Ana L. Mora26Thomas J. Hund27Daniel Gallego-Perez28Kristin I. Stanford29Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterBGPBioBGPBioBGPBioSection on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical SchoolSection on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical SchoolTranslational Research Institute for Metabolism and Diabetes, AdventHealthDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterAbstract 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.https://doi.org/10.1038/s41467-025-62474-7 |
| spellingShingle | 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 12,13-diHOME protects against the age-related decline in cardiovascular function via attenuation of CaMKII Nature Communications |
| title | 12,13-diHOME protects against the age-related decline in cardiovascular function via attenuation of CaMKII |
| title_full | 12,13-diHOME protects against the age-related decline in cardiovascular function via attenuation of CaMKII |
| title_fullStr | 12,13-diHOME protects against the age-related decline in cardiovascular function via attenuation of CaMKII |
| title_full_unstemmed | 12,13-diHOME protects against the age-related decline in cardiovascular function via attenuation of CaMKII |
| title_short | 12,13-diHOME protects against the age-related decline in cardiovascular function via attenuation of CaMKII |
| title_sort | 12 13 dihome protects against the age related decline in cardiovascular function via attenuation of camkii |
| url | https://doi.org/10.1038/s41467-025-62474-7 |
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