Parathyroid hormone induces transition of myofibroblasts in arteriovenous fistula and increases maturation failure

Chung Te Liu, Shih Chang Hsu, Hui Ling Hsieh, Cheng Hsien Chen, Chun You Chen, Yuh Mou Sue, Feng Yen Lin, Chun Ming Shih, Yan Ting Shiu, Po Hsun Huang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Context: 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 is associated with cardiovascular disease. While parathyroid hormone (PTH) has a prosclerotic effect on vascular smooth muscle cells (VSMCs), its role in AVF maturation failure remained unknown. Objective: This work aimed to investigate the association between plasma PTH and AVF maturation. Methods: Patients receiving AVF creation were enrolled retrospectively. A mouse model of secondary hyperparathyroidism and aortocaval AVF was used to investigate the effect of PTH on an AVF lesion. A cell model of VSMCs treated with PTH in a pressurized culture system was used to disclose the signaling pathway underlying the effect of PTH on an AVF lesion. Results: In patients receiving AVF creation, higher PTH was associated with an increased risk for maturation failure. In a mouse model, vascular wall thickness and myofibroblasts of AVF significantly increased with higher PTH. When the same mice were treated with cinacalcet, AVF lesions were attenuated by suppression of PTH. A cell model showed that PTH increased the marker of myofibroblasts, integrin β6 subunit (ITGB6), via the phosphorylated protein kinase B 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. Conclusion: Overall, our results suggest that higher PTH increased the risk of AVF maturation failure through increasing the transition of VSMCs to myofibroblasts. Lowering PTH may be a strategy to enhance AVF maturation.

Original languageEnglish
Pages (from-to)1-15
Number of pages15
JournalEndocrinology
Volume162
Issue number7
DOIs
StatePublished - 1 Jul 2021

Keywords

  • Arteriovenous fistula
  • Fibrosis
  • Hemodialysis
  • Parathyroid hormone

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