Purpose
Arteriovenous fistula (AVF) maturation failure remains a clinical dilemma and its pathobiology is largely unclear. Secondary hyperparathyroidism is a complication of chronic renal failure that associated with cardiovascular disease. While parathyroid hormone (PTH) has prosclerotic effect on vascular smooth muscle cells, its role on AVF maturation failure was unknown.
Methods
Patients receiving AVF creation were enrolled retrospectively to investigate the association between plasma PTH and AVF maturation. A mouse model of secondary hyperparathyroidism and aortocaval AVF was used to investigate the effect of PTH on AVF lesion. A cell model of vascular smooth muscle cell treated with PTH in pressurized culture system was used to disclose the signaling pathway underlying the effect of PTH on AVF lesion.
Results
In patients receiving AVF creation, higher PTH was associated with increased risk for maturation failure. In mouse model, vascular wall thickness and myofibroblasts of AVF significantly increased with higher PTH. When the same mice was treated by cinacalcet, AVF lesions were attenuated by suppression of PTH. Cell model showed that PTH increased the marker of myofibroblasts, integrin β6 subunit (ITGB6) via the phospho-Akt pathway. Finally, in the same model of mice AVF, higher PTH also increased the expression of ITGB6 in the smooth muscle layer of AVF, suggesting the transition to myofibroblast.
Conclusions
Overall, our results suggest that higher PTH increased the risk of AVF maturation failure through increasing the transition of vascular smooth muscle cells to myofibroblasts. Lowering PTH may be a strategy to enhance AVF maturation.