Atrial natriuretic peptide (ANP) is an important hormone in cardiovascular biology. It is activated by the protease corin. In pregnancy, ANP and corin promote uterine spiral artery remodeling, but the underlying mechanism remains unknown. Here we report an ANP function in uterine decidualization and TNF-related apoptosis-inducing ligand–dependent (TRAIL-dependent) death in spiral arterial smooth muscle cells (SMCs) and endothelial cells (ECs). In ANP- or corin-deficient mice, uterine decidualization markers and TRAIL expression were decreased, whereas in cultured human endometrial stromal cells (HESCs), ANP increased decidualization and TRAIL expression. In uterine spiral arteries from pregnant wild-type mice, SMC and EC loss occurred sequentially before trophoblast invasion. In culture, TRAIL from decidualized HESCs induced apoptosis in uterine SMCs, but not in ECs with low TRAIL receptor expression. Subsequently, cyclophilin B was identified from apoptotic SMCs that upregulated endothelial TRAIL receptor and caused apoptosis in ECs. These results indicate that ANP promotes decidualization and TRAIL expression in endometrial stromal cells, contributing to sequential events in remodeling of spiral arteries, including SMC death and cyclophilin B release, which in turn induces TRAIL receptor expression and apoptosis in ECs.

中文翻译：

---

心房利钠肽促进子宫蜕膜化和螺旋动脉重塑中的 TRAIL 依赖性机制

心钠素（ANP）是心血管生物学中的重要激素。它被蛋白酶corin激活。在妊娠期，ANP 和 corin 促进子宫螺旋动脉重塑，但其潜在机制仍不清楚。在这里，我们报告了螺旋动脉平滑肌细胞 (SMC) 和内皮细胞 (EC) 中子宫蜕膜化和 TNF 相关的凋亡诱导配体依赖性（TRAIL 依赖性）死亡中的 ANP 功能。在 ANP 或 corin 缺陷小鼠中，子宫蜕膜标志物和 TRAIL 表达降低，而在培养的人子宫内膜基质细胞 (HESCs) 中，ANP 增加蜕膜化和 TRAIL 表达。在来自怀孕野生型小鼠的子宫螺旋动脉中，SMC 和 EC 损失在滋养层入侵之前依次发生。在文化中，来自蜕膜化 HESCs 的 TRAIL 在子宫 SMCs 中诱导细胞凋亡，但在 TRAIL 受体低表达的 ECs 中没有。随后，从凋亡的 SMC 中鉴定出亲环蛋白 B，其上调内皮 TRAIL 受体并导致 EC 凋亡。这些结果表明，ANP 促进子宫内膜基质细胞中的蜕膜化和 TRAIL 表达，导致螺旋动脉重塑的连续事件，包括 SMC 死亡和亲环蛋白 B 释放，进而诱导 TRAIL 受体表达和 ECs 细胞凋亡。