دورية أكاديمية
Trophoblastic mitochondrial DNA induces endothelial dysfunction and NLRP3 inflammasome activation: Implications for preeclampsia.
| العنوان: | Trophoblastic mitochondrial DNA induces endothelial dysfunction and NLRP3 inflammasome activation: Implications for preeclampsia. |
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| المؤلفون: | Lv Z; Department of Obstetrics, First Affiliated Hospital of Jinan University, 9 Jinsui Road, Guangzhou, China; Department of Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, China., Lv DY; Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China., Meng JY; The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China., Sha XY; Department of Obstetrics, First Affiliated Hospital of Jinan University, 9 Jinsui Road, Guangzhou, China; Department of Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, China., Qian XY; Department of Obstetrics, First Affiliated Hospital of Jinan University, 9 Jinsui Road, Guangzhou, China; Department of Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, China., Chen YS; Department of Obstetrics, First Affiliated Hospital of Jinan University, 9 Jinsui Road, Guangzhou, China; Department of Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, China., Pan XY; Department of Obstetrics, First Affiliated Hospital of Jinan University, 9 Jinsui Road, Guangzhou, China; Department of Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, China., Yu GY; Department of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. Electronic address: guangyuanyu@gwcmc.org., Liu HS; Department of Obstetrics, First Affiliated Hospital of Jinan University, 9 Jinsui Road, Guangzhou, China; Department of Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, China. Electronic address: huishuliu@gwcmc.org. |
| المصدر: | International immunopharmacology [Int Immunopharmacol] 2023 Jan; Vol. 114, pp. 109523. Date of Electronic Publication: 2022 Dec 09. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam ; New York : Elsevier Science, c2001- |
| مواضيع طبية MeSH: | Pre-Eclampsia* , Vascular Diseases*, Female ; Humans ; Mice ; Animals ; Inflammasomes/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Human Umbilical Vein Endothelial Cells ; Trophoblasts/metabolism ; Reactive Oxygen Species/metabolism ; Caspase 1/metabolism ; DNA, Mitochondrial ; Interleukin-1beta/metabolism |
| مستخلص: | Aims: Preeclampsia (PE) is characterised by systemic vascular endothelium dysfunction. Circulating trophoblastic secretions contribute to endothelial dysfunction, resulting in PE; however, the underlying mechanisms remain unclear. Herein, we aimed to determine the potential correlation between the release of trophoblastic mitochondrial deoxyribonucleic acid (DNA) (mtDNA) and endothelium damage in PE. Materials and Methods: Umbilical cord sera and tissues from patients with PE were investigated for inflammasome activation. Following this, trophoblastic mitochondria were isolated from HTR-8/SVneo trophoblasts under 21 % oxygen (O Results: Elevated interleukin (IL)-1β in PE sera was accompanied by NLRP3 inflammasome activation in cord tissues. In vitro and in vivo experiments revealed that the release of trophoblastic mtDNA could damage the endothelium via NLRP3 activation, resulting in the overexpression of NLRP3, caspase-1 p20, IL-1β p17, and gasdermin D (GSDMD); reduced endothelial nitric oxide synthase (eNOS) levels; and impaired vascular relaxation. Flow cytometric analysis confirmed that extensive cell death was induced by mtDNA, and simultaneously, a more pronounced pro-apoptotic effect was caused by hypoxia-treated trophoblastic mtDNA. The NLRP3 knockout or pharmacologic NLRP3 inhibition partially reversed tumour necrosis factor-α (TNF-α) and IL-1β levels and endothelium-dependent vasodilation in mice. Conclusion: These findings demonstrate that trophoblastic mtDNA induced NLRP3/caspase-1/IL-1β signalling activation, eNOS-related endothelial injury, and vasodilation dysfunction in PE. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2022 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Endothelial dysfunction; Inflammation; Mitochondrial DNA; NLRP3 inflammasome; Preeclampsia |
| المشرفين على المادة: | 0 (Inflammasomes) 0 (NLR Family, Pyrin Domain-Containing 3 Protein) 0 (Reactive Oxygen Species) EC 3.4.22.36 (Caspase 1) 0 (DNA, Mitochondrial) 0 (Interleukin-1beta) 0 (Nlrp3 protein, mouse) |
| تواريخ الأحداث: | Date Created: 20221212 Date Completed: 20230105 Latest Revision: 20230111 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.intimp.2022.109523 |
| PMID: | 36508916 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1878-1705 |
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| DOI: | 10.1016/j.intimp.2022.109523 |