Abstract
Abstract only Objective: Collagen VIII is a basement collagen upregulated in processes of vascular remodeling. We recently demonstrated the association of increased COL8A1 expression and arteriovenous fistula failure in a human cohort. This study analyzed the effect of loss of collagen VIII in a murine arteriovenous fistula model. Methods: Arteriovenous fistulas were created between the external jugular vein and common carotid artery of 5/6 nephrectomized Col8a1/a2 null mice and wild type controls (n=8-9 per group). Intimal hyperplasia was quantified in Masson’s trichrome stained sections. Inflammation was evaluated by immunofluorescence using anti-galectin 3 (Mac2) antibodies and expressed as % positive cells/total cells. Results: AVF cross-sections from collagen VIII null mice demonstrated a significant reduction in intimal hyperplasia compared to controls (7.6 vs 107.8, p = 0.004). AVF from collagen VIII null mice also presented a significantly lower proportion of infiltrated macrophages compared to fistulas in wild type mice (1.00 vs. 6.05%, p=0.004). Conclusions: This study shows for the first time that absence of collagen VIII improves postoperative remodeling of murine AVF. Importantly, our findings suggest a dual role of collagen VIII in vascular inflammation and wall remodeling.