Department of Obstetrics and Gynecology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Immun Inflamm Dis. 2022 Sep;10(9):e678. doi: 10.1002/iid3.678.
This study was intended to investigate the effect of SAMD1 on antiphospholipid syndrome (APS)-induced vascular injury in human umbilical vein endothelial cells (HUVECs) and pregnancy complications in mice.
The expression of SAMD1 in APS patients and healthy controls was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Anti-B GPI and anticardiolipin antibody (ACA) levels were tested by enzyme-linked immunosorbent assay, MMP-9, iNOS, ICAM-1, and MCP-1 mRNA and protein levels determined by qRT-PCR and Western blot, cellular senescence detected by β-galactosidase staining, cell proliferation ability detected by CCK-8 assay, cell viability detected by trypan blue staining, cell mobility detected by Transwell, and cell angiogenesis ability detected by matrigel tube formation assay. An APS pregnant mouse model was constructed, and the embryo absorption rate was calculated.
SAMD1 expression was low in serum of APS patients, which was correlated with the history of thrombosis and the number of adverse pregnancies. Anti-B GPI and ACA levels were increased in APS. The expressions of MMP-9, iNOS, ICAM-1, and MCP-1 were also significantly upregulated in HUVECs treated with APS serum. APS promoted HUVEC senescence and inhibited cell proliferation, migration, and angiogenesis. Overexpression of SAMD1 reversed the above results. Experiments on the APS pregnant mouse model confirmed that overexpression of SAMD1 reduced the rate of fetal loss.
SAMD1 may reduce APS-induced vascular injury and embryo loss by regulating cellular senescence, proliferation, migration, and angiogenesis.
本研究旨在探讨 SAMD1 对抗磷脂综合征（APS）诱导的人脐静脉内皮细胞（HUVEC）血管损伤及小鼠妊娠并发症的影响。
通过实时定量聚合酶链反应（qRT-PCR）检测 APS 患者和健康对照者中 SAMD1 的表达。采用酶联免疫吸附试验（ELISA）检测抗-β 2 糖蛋白 I（anti-B GPI）和抗心磷脂抗体（ACA）水平，qRT-PCR 和 Western blot 检测 MMP-9、iNOS、ICAM-1 和 MCP-1 的 mRNA 和蛋白水平，β-半乳糖苷酶染色检测细胞衰老，CCK-8 检测细胞增殖能力，台盼蓝染色检测细胞活力，Transwell 检测细胞迁移能力，Matrigel 管形成实验检测细胞血管生成能力。构建 APS 妊娠小鼠模型，计算胚胎吸收率。
APS 患者血清中 SAMD1 表达降低，与血栓形成史和不良妊娠次数相关。APS 患者血清中抗-B GPI 和 ACA 水平升高。APS 血清处理后的 HUVECs 中 MMP-9、iNOS、ICAM-1 和 MCP-1 的表达也明显上调。APS 促进 HUVEC 衰老并抑制细胞增殖、迁移和血管生成。SAMD1 的过表达逆转了上述结果。APS 妊娠小鼠模型实验证实，SAMD1 的过表达降低了胎儿丢失率。
SAMD1 可能通过调节细胞衰老、增殖、迁移和血管生成，减轻 APS 诱导的血管损伤和胚胎丢失。
