Summary of project PR002168
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002168. The data can be accessed directly via it's Project DOI: 10.21228/M8CR8X This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002168 |
| Project DOI: | doi: 10.21228/M8CR8X |
| Project Title: | Arachidonic acid fuels inflammation by unlocking 5-LOX in macrophages after myocardial infarction to promote cardiac dysfunction |
| Project Summary: | An overactive inflammatory response and immune cell infiltration in myocardial infarction (MI) impairs tissue repair. Arachidonic acid (AA) metabolites act as important sources of inflammatory mediators in cardiac tissue. We investigated the mechanisms underlying the AA cascade-mediated inflammatory response after MI. Metabolomics analyses revealed that the 5-lipoxygenase (5-LOX)-dependent AA metabolic pathway derivative leukotriene B4 (LTB4) accumulated in large quantities after MI. Elevated levels of AA in vivo after MI facilitated the recruitment of protein phosphatase 5 (PP5) into the nucleus by binding PP5 to its nuclear transporter receptor karyopherin subunit alpha 1. On entering the nucleus, PP5 directly dephosphorylated 5-LOX at Thr218, promoting the production of the proinflammatory mediator LTB4 by macrophages. Transgenic mice were created with a population of cardiac resident macrophages with a mutation at 5-LOX Thr218. Single-cell transcriptomics showed that these cells overexpressed CXC-chemokine ligand 13 and actively recruited B cells to the heart, exacerbating tissue inflammation. In a UK Biobank cohort, the PP5 E76D mutation was found to be associated with complications after acute MI. Overall, our results have elucidated a conserved role for 5-LOX-phosphorylation-regulated LTB4 levels in MI and identified PP5 as a potential therapeutic target for the treatment of MI. |
| Institute: | Tianjin Medical University |
| Last Name: | Song |
| First Name: | Jiawei |
| Address: | Tianjin Medical University, Tianjin, China., Tianjin, Tianjin, 300070, China |
| Email: | sjw808@tmu.edu.cn |
| Phone: | 15309216256 |
Summary of all studies in project PR002168
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003524 | Arachidonic acid fuels inflammation by unlocking 5-LOX in macrophages after myocardial infarction | Homo sapiens | Tianjin Medical University | MS | 2025-11-14 | 1 | 272 | Uploaded data (45.2M)* |
| ST003534 | Metabolomic analysis of altered arachidonic acid metabolism in mouse heart tissue after myocardial infarction | Mus musculus | Tianjin Medical University | MS | 2025-11-14 | 1 | 70 | Uploaded data (10.4M)* |
