Autotaxin Inhibition Reduces Post-Ischemic Myocardial Inflammation via Epigenetic Gene Modifications.

Autor: Guo LZ; Department of Biology, University of Kentucky, Lexington, KY, USA., Tripathi H; Michigan Medicine, Division of Internal Medicine Cardiology, University of Michigan, and the Ann Arbor VA Healthcare System, Ann Arbor, MI, USA., Gao E; Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA., Tarhuni WM; Canadian Cardiac Research Center, Department of Internal Medicine, Division of Cardiology, University of Saskatchewan, Saskatoon, SK, Canada., Abdel-Latif A; Michigan Medicine, Division of Internal Medicine Cardiology, University of Michigan, and the Ann Arbor VA Healthcare System, Ann Arbor, MI, USA. aalatif@umich.edu.
Jazyk: angličtina
Zdroj: Stem cell reviews and reports [Stem Cell Rev Rep] 2024 Oct; Vol. 20 (7), pp. 1971-1980. Date of Electronic Publication: 2024 Jul 10.
DOI: 10.1007/s12015-024-10759-7
Abstrakt: Myocardial infarction (MI) triggers a complex inflammatory response that is essential for cardiac repair but can also lead to adverse outcomes if left uncontrolled. Recent studies have highlighted the importance of epigenetic modifications in regulating post-MI inflammation. This study investigated the role of the autotaxin (ATX)/lysophosphatidic acid (LPA) signaling axis in modulating myocardial inflammation through epigenetic pathways in a mouse model of MI. C57BL/6 J mice underwent left anterior descending coronary artery ligation to induce MI and were treated with the ATX inhibitor, PF-8380, or vehicle. Cardiac tissue from the border zone was collected at 6 h, 1, 3, and 7 days post-MI for epigenetic gene profiling using RT 2 Profiler PCR Arrays. The results revealed distinct gene expression patterns across sham, MI + Vehicle, and MI + PF-8380 groups. PF-8380 treatment significantly altered the expression of genes involved in inflammation, stress response, and epigenetic regulation compared to the vehicle group. Notably, PF-8380 downregulated Hdac5, Prmt5, and Prmt6, which are linked to exacerbated inflammatory responses, as early as 6 h post-MI. Furthermore, PF-8380 attenuated the reduction of Smyd1, a gene important in myogenic differentiation, at 7 days post-MI. This study demonstrates that the ATX/LPA signaling axis plays a pivotal role in modulating post-MI inflammation via epigenetic pathways. Targeting ATX/LPA signaling may represent a novel therapeutic strategy to control inflammation and improve outcomes after MI. Further research is needed to validate these findings in preclinical and clinical settings and to elucidate the complex interplay between epigenetic mechanisms and ATX/LPA signaling in the context of MI.
(© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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