Novel treatment avenues for uterine leiomyoma: A new implication for Endothelin?

CYR61 (cysteine-rich angiogenic inducer 61), an angiogenic factor whose expression is decreased in fibroids. The aim of this study was to determine if CYR61 secretion in smooth muscle cells is regulated by hypoxia and through the endothelin A (ETA) receptor. Smooth muscle cells from fibroids (fSMC) and the adjacent myometrium smooth muscle cells (mSMC) were extracted from 10 women undergoing hysterectomy for uterine fibroids and cultured with or without 1.0µM of an ETA receptor antagonist for 24hrs under either normal or hypoxic oxygen conditions. Cellular secretion of endothelin-1 (ET-1) and CYR61 were measured via enzyme linked immunosorbent assay in the cell culture media. Smooth muscle cells were collected to determine cell proliferation and CYR61 protein expression via western blot. ET-1 secretion was significantly increased in fSMC and was decreased with blockade of the ETA receptor under both normoxia (p=0.0004) and hypoxia (p=0.008). CYR61 expression was decreased in fSMCs and significantly increased with blockade of the ETA receptor under hypoxia (p=0.04). Cell proliferation decreased with ETA blockade under normoxia (p=0.0001) and hypoxia (p=0.001). These results suggest that suppression of CYR61 secretion in fSMC is regulated by the ET-1 and that blockade with ETA could be considered for a future treatment option.

Source: Clinical Science - October 9, 2018 Category: Biomedical Science Authors: Wallace, K., Chatman, K., Johnson, V., Brookins, A., Rushing, J., LaMarca, B. Tags: PublishAheadOfPrint Source Type: research