Characterization of central venous stenosis induced by indwelling catheter and balloon injury in a rabbit model: angiographic, histological, and molecular evaluations

BACKGROUND: Central venous stenosis (CVS) is a significant complication in patients undergoing hemodialysis. Although mechanical injury and foreign body reactions are known triggers, the differential pathophysiological mechanisms underlying CVS induced by transient balloon injury and chronic indwelling catheters remain unclear. This study compared stenotic phenotypes and molecular pathways in rabbit models of balloon-induced (Ap) and catheter-related (Ac) CVS. METHODS: Rabbit models were established using balloon dilation (Ap group, n = 9) or indwelling catheter implantation (Ac group, n = 10) in the anterior vena cava. Vessel patency was assessed using serial angiography on day 30. Histomorphological changes were quantified using HE and Masson's trichrome staining. The molecular profile of vascular remodeling was characterized by immunohistochemical analysis of α-SMA, TGF-β1, MMP-2, and CD31. RESULTS: Angiography revealed a disparity in stenosis incidence and severity between the two groups. The Ac group exhibited a 100% incidence with severe luminal narrowing (median stenosis rate: 66.5%), whereas the Ap group showed a lower incidence (33.3%) and mild heterogeneous stenosis (median: 3.5%). Histologically, the Ac group demonstrated a 3.5-fold increase in intimal thickness (416.7 ± 10.8 μm vs. 119.7 ± 7.2 μm, P < 0.01) and extensive collagen deposition (41.7% vs. 14.7%, P < 0.01). The Ac group was characterized by fibrin sheath formation and significantly upregulated expression of profibrotic and remodeling markers (α-SMA, TGF-β1, MMP-2, and CD31). CONCLUSION: Indwelling catheters induce a more severe and uniform stenotic phenotype than transient mechanical injury, owing to exacerbated fibrosis and vascular remodeling pathways involving TGF-β1 and MMP-2. Hence, the pathophysiology of catheter-related CVS differs from that of balloon-induced injury, highlighting the need for targeted antifibrotic therapies for catheter-related complications.