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Editorial
. 2023 Jan 6;132(1):30-33.
doi: 10.1161/CIRCRESAHA.122.322272. Epub 2023 Jan 5.

Cell-Based Phenotypic Screen for Antifibrotic Compounds Targets Eicosanoid Metabolism

Janet K Lighthouse  1   2 , Eric M Small  2   3   4   5
Affiliations
Editorial

Cell-Based Phenotypic Screen for Antifibrotic Compounds Targets Eicosanoid Metabolism

Janet K Lighthouse et al. Circ Res. .
No abstract available

Keywords: Editorials; extracellular matrix; fibrosis; heart failure; myocardial infarction.

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Figures

Figure.
Figure.
SW033291 inhibits 15-PGDH to promote eicosanoid secretion and signaling in fibroblasts. Fibroblasts activated by TGF-β secrete extracellular matrix and pro-inflammatory factors that contribute to diastolic dysfunction. Activated fibroblasts can be reverted back to a more quiescent phenotype by inhibition of 15-PGDH (15-hydroxyprostaglandin dehydrogenase) with SW033291. Inhibition of 15-PGDH reduces eicosanoid degradation, promoting the secretion of PGE2 and 12[S]-HETE by cardiac fibroblasts. 12[S]-HETE subsequently activates the orphan GPCR receptor GPR31 to stimulate ERK1/2 signaling and ameliorate the fibrotic phenotype.
See this image and copyright information in PMC

Comment on

  • Inhibition of Eicosanoid Degradation Mitigates Fibrosis of the Heart.
    Rubino M, Travers JG, Headrick AL, Enyart BT, Lemieux ME, Cavasin MA, Schwisow JA, Hardy EJ, Kaltenbacher KJ, Felisbino MB, Jonas E, Ambardekar AV, Bristow MR, Koch KA, McKinsey TA. Rubino M, et al. Circ Res. 2023 Jan 6;132(1):10-29. doi: 10.1161/CIRCRESAHA.122.321475. Epub 2022 Dec 8. Circ Res. 2023. PMID: 36475698

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