Academic Journal
PCSK6 is a novel regulator of venous smooth muscle cell function in arteriovenous fistula remodeling.
| Τίτλος: | PCSK6 is a novel regulator of venous smooth muscle cell function in arteriovenous fistula remodeling. |
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| Συγγραφείς: | Guo X; Department of Vascular Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Vascular Surgery, Ningbo Hangzhou Bay Hospital, Ningbo, China., Cao R; Department of Vascular Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Wang T; Department of Biomedical Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, USA., Zhang L; Department of Vascular Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Li Y; Department of Vascular Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. |
| Πηγή: | Renal failure [Ren Fail] 2026 Dec; Vol. 48 (1), pp. 2663246. Date of Electronic Publication: 2026 May 05. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Informa Healthcare Country of Publication: England NLM ID: 8701128 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-6049 (Electronic) Linking ISSN: 0886022X NLM ISO Abbreviation: Ren Fail Subsets: MEDLINE |
| Imprint Name(s): | Publication: London : Informa Healthcare Original Publication: New York, N.Y. : M. Dekker, c1987- |
| Ιατρικοί όροι (MeSH): | Muscle, Smooth, Vascular*/pathology , Muscle, Smooth, Vascular*/metabolism , Muscle, Smooth, Vascular*/cytology , Neointima*/pathology , Neointima*/metabolism , Proprotein Convertases*/metabolism , Proprotein Convertases*/genetics , Myocytes, Smooth Muscle*/metabolism , Arteriovenous Shunt, Surgical*/adverse effects , Subtilisins*/metabolism , Subtilisins*/genetics , Vascular Remodeling*, STAT1 Transcription Factor/metabolism ; Extracellular Matrix/metabolism ; Animals ; Humans ; Mice ; Male ; Mice, Knockout ; Cell Proliferation ; Hyperplasia ; Renal Dialysis ; Cell Movement ; Serine Endopeptidases |
| Περίληψη: | The arteriovenous fistula (AVF), the preferred vascular access for hemodialysis, is limited by neointimal hyperplasia. Although proprotein convertase subtilisin/kexin type 6 (PCSK6) is involved in vascular smooth muscle cell (VSMC) activation, its role in AVF stenosis is unclear. PCSK6 expression was significantly upregulated in VSMCs of human and murine stenotic AVFs and correlated with the severity of neointimal hyperplasia. In vitro, PCSK6 overexpression promoted VSMC proliferation, migration, contractility, and extracellular matrix (ECM) synthesis, whereas PCSK6 knockdown suppressed these processes. Mechanistically, PCSK6 directly interacted with STAT1 and enhanced its phosphorylation, with STAT1 inhibition reversing PCSK6-driven effects. In vivo, smooth muscle cell-specific PCSK6 knockout in mice on a high-glucose diet attenuated neointimal formation, improved AVF lumen diameter and blood flow, and enhanced vasodilation. In conclusion, PCSK6 drives AVF neointimal hyperplasia by binding and activating STAT1 to promote VSMC phenotypic switching and ECM remodeling, identifying the PCSK6/STAT1 axis as a novel mechanism and potential therapeutic target for preventing AVF failure. |
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| Contributed Indexing: | Keywords: Arteriovenous fistula; PCSK6; STAT1; vascular remodeling |
| Substance Nomenclature: | EC 3.4.21.- (Proprotein Convertases) 0 (STAT1 Transcription Factor) EC 3.4.21.- (PCSK6 protein, human) 0 (STAT1 protein, human) EC 3.4.21.- (Pcsk6 protein, mouse) EC 3.4.21.- (Subtilisins) EC 3.4.21.- (Serine Endopeptidases) |
| Entry Date(s): | Date Created: 20260505 Date Completed: 20260716 Latest Revision: 20260813 |
| Update Code: | 20260813 |
| PubMed Central ID: | PMC13148085 |
| DOI: | 10.1080/0886022X.2026.2663246 |
| PMID: | 42087061 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1525-6049 |
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| DOI: | 10.1080/0886022X.2026.2663246 |