| Autor: |
Yuning Gao, Tianshi Chen, Lei Hong |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Heliyon, Vol 10, Iss 7, Pp e27626- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2405-8440 |
| DOI: |
10.1016/j.heliyon.2024.e27626 |
| Popis: |
Objective: Stent intimal hyperplasia leads to in stent restenosis and thrombosis. This study determined whether Fibulin-1 activity in smooth muscle cells (SMCs) contributes to stent restenosis or thrombosis. Methods: Stent implantation was conducted in a pig model. Target vessel samples were stained and analyzed by protein mass spectrometry. Cell experiments and Fibulin-1 SMC specific knockout mice (Fbln1SMKO) were used to investigate the mechanism of Fibulin-1 induced SMC proliferation and thrombosis. Results: SMC proliferation and phenotypic transition are the main pathological changes of intimal hyperplasia in venous stents. Protein mass spectrometry analysis revealed a total of 67 upregulated proteins and 39 downregulated proteins in intimal hyperplasia after stent implantation compared with normal iliac vein tissues. Among them, Fibulin-1 ranked among the top proteins altered. Fibulin-1 overexpressing human SMCs (Fibulin-1-hSMCs) showed increased migration and phenotypic switching from contractile to secretory type and Fibulin-1 inhibition decreased the activity of SMCs. Mechanistically, Fibulin-1-hSMCs displayed increased levels of angiotensin converting enzyme (ACE) expression and angiotensin II signaling. Inhibition of ACE or angiotensin II signaling alleviated the migration of Fibulin-1-hSMCs. Using Fibulin-1 SMC specific knockout mice (Fbln1SMKO) and venous thrombosis model, we demonstrated that Fibulin-1 deletion attenuated intimal SMCs proliferation and thrombosis. Further, Fibulin-1 concentration was high in iliac vein compression syndrome (IVCS) patients treated with stent and was an independent predictor of venous insufficiency. Conclusions: Fibulin-1 promotes SMC proliferation partially through ACE secretion and angiotensin II signaling after stent implantation. Fibulin-1 plays a role in venous insufficiency syndrome, implicating the protein in the detection and treatment of IVCS. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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