Academic Journal
Endothelial Matrin-3 Limits Cellular Senescence and Lipid Dysregulation to Protect Against Murine Atherosclerosis.
| Τίτλος: | Endothelial Matrin-3 Limits Cellular Senescence and Lipid Dysregulation to Protect Against Murine Atherosclerosis. |
|---|---|
| Συγγραφείς: | Cheng X; Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, Nebraska, USA., Tanni FY; Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, Nebraska, USA., Zoni RN; Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, Nebraska, USA., Abdollahi E; Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, Nebraska, USA., Childs E; Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, Nebraska, USA., Sun X; Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.; Nebraska Center for the Prevention of Obesity Diseases Through Dietary Molecules, University of Nebraska-Lincoln, Lincoln, Nebraska, USA. |
| Πηγή: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2026 Oct 31; Vol. 40 (20), pp. e72396. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Federation of American Societies for Experimental Biology Country of Publication: United States NLM ID: 8804484 Publication Model: Print Cited Medium: Internet ISSN: 1530-6860 (Electronic) Linking ISSN: 08926638 NLM ISO Abbreviation: FASEB J Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2020- : [Bethesda, Md.] : Hoboken, NJ : Federation of American Societies for Experimental Biology ; Wiley Original Publication: [Bethesda, Md.] : The Federation, [c1987- |
| Ιατρικοί όροι (MeSH): | Atherosclerosis*/metabolism , Atherosclerosis*/pathology , Atherosclerosis*/prevention & control , RNA-Binding Proteins*/metabolism , RNA-Binding Proteins*/genetics , Nuclear Matrix-Associated Proteins*/metabolism , Nuclear Matrix-Associated Proteins*/genetics , Endothelial Cells*/metabolism , Cellular Senescence* , Lipid Metabolism*, Animals ; Mice ; Humans ; Mice, Knockout ; Mice, Inbred C57BL |
| Περίληψη: | Matrin-3 is a DNA- and RNA-binding protein implicated in cardiovascular development. However, the role of endothelial Matrin-3 in atherosclerosis has not been previously studied. Here, we found that Matrin-3 silencing induces endothelial senescence, characterized by reduced cell proliferation, increased senescence-associated β-galactosidase activity, and impaired mitochondrial function in vitro. Quantitative proteomics and bulk RNA-sequencing identified hundreds of differentially expressed genes and proteins in human endothelial cells. Bioinformatic analyses revealed enrichment of pathways related to DNA replication, p53 signaling, cell-cycle regulation, and cellular senescence. To examine the role of endothelial Matrin-3 in atherosclerosis, we generated Matrin-3 floxed mice on a low-density lipoprotein receptor-knockout background and crossed them with mice carrying an endothelial cell-specific, tamoxifen-inducible Cre driver. In a mouse model of atherosclerosis, endothelial cell-specific Matrin-3 deficiency increased atherosclerotic lesion area by 1.41-fold and was associated with increased plasma low-density lipoprotein cholesterol and triglycerides, increased hepatic cholesterol and triglycerides, and substantial transcriptional alterations in the aortic intima. Endothelial Matrin-3 deficiency also induced hepatic steatosis, fibrosis, inflammation, and endothelial senescence. Single-nucleus RNA-sequencing of the liver further revealed transcriptional reprogramming of hepatocytes, including alterations in pathways related to lipid metabolism, inflammation, and constitutive androstane receptor signaling, consistent with a functional link between endothelial Matrin-3 deficiency and hepatocyte transcriptional responses. Finally, Matrin-3 expression was reduced in mouse and human atherosclerotic plaques. Together, these findings identify endothelial Matrin-3 as an important regulator of endothelial senescence and lipid homeostasis and demonstrate that endothelial Matrin-3 deficiency is associated with both local vascular alterations and systemic metabolic dysfunction in atherosclerosis. (© 2026 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.) |
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| Grant Information: | R01 HL150536 United States HL NHLBI NIH HHS; HL150536 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI); R01 DK145704 United States DK NIDDK NIH HHS; T32 GM136593 United States GM NIGMS NIH HHS; P30GM154608 HHS | NIH | National Institute of General Medical Sciences (NIGMS); T32 2T32GM136593-06 HHS | NIH | National Institute of General Medical Sciences (NIGMS); DK145704 HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); P30 GM154608 United States GM NIGMS NIH HHS; R01 HL175569 United States HL NHLBI NIH HHS; HL175569 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) |
| Contributed Indexing: | Keywords: Matrin‐3; atherosclerosis; cellular senescence; vascular endothelium |
| Substance Nomenclature: | 0 (RNA-Binding Proteins) 0 (MATR3 protein, human) 0 (Nuclear Matrix-Associated Proteins) |
| Entry Date(s): | Date Created: 20261017 Date Completed: 20261017 Latest Revision: 20261022 |
| Update Code: | 20261022 |
| PubMed Central ID: | PMC13675935 |
| DOI: | 10.1096/fj.202602809RR |
| PMID: | 42891558 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1530-6860 |
|---|---|
| DOI: | 10.1096/fj.202602809RR |