Free fatty acid receptor 4 in cardiac myocytes ameliorates ischemic cardiomyopathy
Clicks: 1
ID: 325181
2026
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This
article has not been analysed, so there is no overall score —
reader engagement is measured and shown alongside.
Reader Engagement
0.0
/100
1 views
0 readers
AI Quality Assessment
Not analyzed
Readership in this journal
Ranked #44 of 102 articles by views in cardiovascular research
Most read
Least read
Bar heights use a square-root scale.
Mint this article as an NFT
Not yet mintedCreate a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.
5
SUSD
one-off · no wallet required
Abstract
AIMS: Free fatty acid receptor 4 (Ffar4) is a receptor for long-chain fatty acids that attenuates heart failure driven by increased afterload. Recent findings suggest that Ffar4 prevents ischemic injury in brain, liver, and kidney, and therefore, we hypothesized that Ffar4 would attenuate cardiac ischemic injury. METHODS AND RESULTS: Using a mouse model of ischemia-reperfusion (I/R), we found in mice with systemic deletion of Ffar4 (Ffar4KO), loss of Ffar4 impaired the recovery of left ventricular systolic function post-I/R with no effect on initial infarct size. To identify potential mechanistic explanations for the cardioprotective effects of Ffar4, we performed bulk RNAseq to compare the transcriptomes from wild-type (WT) and Ffar4KO infarcted myocardium 3-days post-I/R. The transcriptome analysis identified the downregulation of several metabolic pathways suggesting impaired mitochondrial function in the infarcted Ffar4KO myocardium. Mechanistically, basal mitochondrial function and morphology were impaired in cardiac myocytes from Ffar4KO mice corroborating the results of the transcriptome analysis. Interestingly, phosphodiesterase 6c (Pde6c), which degrades cGMP, was the most upregulated gene in the Ffar4KO heart. Further, the soluble guanylyl cyclase stimulator, vericiguat, failed to increase cGMP in Ffar4KO cardiac myocytes, suggesting increased phosphodiesterase activity. Finally, cardiac myocyte-specific overexpression of Ffar4 in vivo and activation of Ffar4 in cardiac myocytes in vitro attenuated ischemic/hypoxic injury respectively. CONCLUSIONS: Our results define a novel protective role for Ffar4 in cardiac myocytes to attenuate systolic dysfunction and prevent ischemic cardiomyopathy post I/R by preserving mitochondrial function and activating cGMP signaling.
| Reference Key |
openalex_W4394852328
Use this key to autocite in the manuscript while using
SciMatic Manuscript Manager or Thesis Manager
|
|---|---|
| Authors | Michael J. Zhang, Sara J. Puccini, Sergey Karachenets, Dylan J. Gyberg, Shanmugasundaram Pakkiriswami, Megan Sumera, Ryan Gemilere, Natalie L. Weir, Sebastian L Torres, Chastity L. Healy, Brian Harsch, Steven C. Wu, Julia Liu, Gregory C. Shearer, Timothy D. O’Connell |
| Journal | cardiovascular research |
| Year | 2026 |
| DOI |
10.1093/cvr/cvag175
|
| URL | |
| Keywords | Keywords not found |
Citations
No citations found. To add a citation, contact the admin at info@scimatic.org
Comments
No comments yet. Be the first to comment on this article.