Relaxin receptor deficiency promotes vascular inflammation and impairs outward remodeling in arteriovenous fistulas

The pathophysiology of arteriovenous fistula (AVF) maturation failure is not completely understood but impaired outward remodeling (OR) and intimal hyperplasia are thought to be contributors. This adverse vascular response after AVF surgery results from interplay between vascular smooth muscle cells (VSMCs), the extracellular matrix (ECM), and inflammatory cells. Relaxin (RLN) is a hormone that acts on the vasculature via interaction with RLN/insulin-like peptide family receptor 1 (RXFP1), resulting in vasodilatation, ECM remodeling, and decreased inflammation. In the present study, we evaluated the consequences of RXFP1 knockout (Rxfp1−/−) on AVF maturation in a murine model of AVF failure. Rxfp1−/− mice showed a 22% decrease in vessel size at the venous outflow tract 14 d after AVF surgery. Furthermore, a 43% increase in elastin content was observed in the lesions of Rxfp1−/− mice and coincided with a 41% reduction in elastase activity. In addition, Rxfp1−/− mice displayed a 6-fold increase in CD45+ leu...