دورية أكاديمية
Non-Interferon-Dependent Role of STING Signaling in Pulmonary Hypertension.
| العنوان: | Non-Interferon-Dependent Role of STING Signaling in Pulmonary Hypertension. |
|---|---|
| المؤلفون: | Pham AT; Department of Medicine, University of Florida College of Medicine, Gainesville., Oliveira AC; Department of Medicine, University of Florida College of Medicine, Gainesville., Albanna M; Department of Medicine, University of Florida College of Medicine, Gainesville., Alvarez-Castanon J; Department of Medicine, University of Florida College of Medicine, Gainesville., Dupee Z; Department of Medicine, University of Florida College of Medicine, Gainesville., Patel D; Department of Medicine, University of Florida College of Medicine, Gainesville., Fu C; Department of Medicine, University of Florida College of Medicine, Gainesville., Mukhsinova L; Department of Medicine, University of Florida College of Medicine, Gainesville., Nguyen A; Department of Medicine, University of Florida College of Medicine, Gainesville., Jin L; Department of Medicine, University of Florida College of Medicine, Gainesville., Bryant AJ; Department of Medicine, University of Florida College of Medicine, Gainesville. |
| المصدر: | Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2024 Jan; Vol. 44 (1), pp. 124-142. Date of Electronic Publication: 2023 Nov 09. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 9505803 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4636 (Electronic) Linking ISSN: 10795642 NLM ISO Abbreviation: Arterioscler Thromb Vasc Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1998- : Baltimore, Md. : Lippincott Williams & Wilkins Original Publication: Dallas, TX : American Heart Association, c1995- |
| مواضيع طبية MeSH: | Hypertension, Pulmonary*/genetics , Interferon Type I*/metabolism, Humans ; Animals ; Mice ; Vascular Endothelial Growth Factor A ; Leukocytes, Mononuclear/metabolism ; Signal Transduction |
| مستخلص: | Background: Patients with constitutive activation of DNA-sensing pathway through stimulator of IFN (interferon) genes (STING), such as those with STING-associated vasculopathy with onset in infancy, develop pulmonary hypertension (PH). However, the role of STING signaling in general PH patients is heretofore undescribed. Here, we seek to investigate the role of STING in PH development. Methods: STING expression in patient lung samples was examined. PH was induced in global STING-deficient mice and global type I IFN receptor 1-deficient mice using bleomycin or chronic hypoxia exposure. PH development was evaluated by right ventricular systolic pressure and Fulton index, with additional histological and flow cytometric analysis. VEGF (vascular endothelial growth factor) expression on murine immune cells was quantified and evaluated with multiplex and flow cytometry. Human myeloid-derived cells were differentiated from peripheral blood mononuclear cells and treated with either STING agonist or STING antagonist for evaluation of VEGF secretion. Results: Global STING deficiency protects mice from PH development, and STING-associated PH seems independent of type I IFN signaling. Furthermore, a role for STING-VEGF signaling pathway in PH development was demonstrated, with altered VEGF secretion in murine pulmonary infiltrated myeloid cells in a STING-dependent manner. In addition, pharmacological manipulation of STING in human myeloid-derived cells supports in vivo findings. Finally, a potential role of STING-VEGF-mediated apoptosis in disease development and progression was illustrated, providing a roadmap toward potential therapeutic applications. Conclusions: Overall, these data provide concrete evidence of STING involvement in PH, establishing biological plausibility for STING-related therapies in PH treatment. Competing Interests: Disclosures None. |
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| معلومات مُعتمدة: | R01 HL142776 United States HL NHLBI NIH HHS; R01 HL142887 United States HL NHLBI NIH HHS |
| فهرسة مساهمة: | Keywords: hypertension, pulmonary; interferon; treatment |
| المشرفين على المادة: | 0 (Vascular Endothelial Growth Factor A) 0 (Interferon Type I) |
| تواريخ الأحداث: | Date Created: 20231109 Date Completed: 20231229 Latest Revision: 20240226 |
| رمز التحديث: | 20240226 |
| مُعرف محوري في PubMed: | PMC10872846 |
| DOI: | 10.1161/ATVBAHA.123.320121 |
| PMID: | 37942608 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1524-4636 |
|---|---|
| DOI: | 10.1161/ATVBAHA.123.320121 |