Gu Yang, Thompson Donna, Xu Jie, Lewis David F, Morgan John A, Cooper Danielle B, McCathran Charles E, Wang Yuping
Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center - Shreveport, LA, USA.
Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center - Shreveport, LA, USA; Department of Physiology, Harbin Medical University, Harbin, Heilongjiang, China.
Pregnancy Hypertens. 2018 Jan;11:1-6. doi: 10.1016/j.preghy.2017.12.001. Epub 2017 Dec 7.
Corin is a serine protease that converts pro-atrial natriuretic peptide (pro-ANP) to atrial natriuretic peptide (ANP), a cardiac hormone that regulates salt-water balance and blood pressure. ANP is degraded by natriuretic peptide receptor (NPR). This study was to determine if aberrant pro-ANP/corin/NPR signaling is present in maternal vascular system in preeclampsia.
Maternal venous blood was obtained from 197 pregnant women (84 normotensive, 16 complicated with chronic hypertension (CHT), 11 mild and 86 severe preeclampsia). Plasma corin and pro-ANP concentrations were measured by enzyme-linked immunosorbent assay. Maternal subcutaneous fat tissue was obtained from 12 pregnant women with cesarean section delivery (6 normotensive and 6 preeclampsia). Vascular ANP and its receptors NPR-A, NPR-B, and NPR-C expression were examined by immunostaining of paraffin embedded subcutaneous fat tissue sections.
Corin concentrations were significantly higher in mild (2.78 ± 0.67 ng/ml, p < .05) and severe (2.53 ± 0.18 ng/ml, p < .01) preeclampsia than in normotensive (1.58 ± 0.08 ng/ml) and CHT (1.55 ± 0.20 ng/ml) groups. Pro-ANP concentrations were significantly higher in CHT (1.59 ± 0.53 ng/ml, p < .05) and severe preeclampsia (1.42 ± 0.24 ng/ml, p < .01) than in normotensive (0.48 ± 0.06 ng/ml) and mild preeclampsia (0.52 ± 0.09 ng/ml) groups. ANP and NPR-B expression was undetectable in maternal vessels from normotensive and preeclamptic pregnancies, but reduced NPR-A expression and increased NPR-C expression was found in maternal vessel endothelium in preeclampsia.
ANP is a vasodilator and NPR-C is a clearance receptor for ANP. The finding of upregulation of NPR-C expression suggests that circulating ANP clearance or degradation is increased in preeclampsia. These results also suggest that pro-ANP/corin/NPR signaling is dominant in the vascular system in preeclampsia.
Corin是一种丝氨酸蛋白酶,可将前心钠素(pro-ANP)转化为心钠素(ANP),后者是一种调节水盐平衡和血压的心脏激素。ANP由利钠肽受体(NPR)降解。本研究旨在确定子痫前期孕妇血管系统中是否存在异常的pro-ANP/corin/NPR信号通路。
采集197名孕妇(84名血压正常者、16名合并慢性高血压(CHT)者、11名轻度子痫前期患者和86名重度子痫前期患者)的母体外周静脉血。采用酶联免疫吸附测定法检测血浆corin和pro-ANP浓度。从12名剖宫产分娩的孕妇(6名血压正常者和6名子痫前期患者)获取母体皮下脂肪组织。通过对石蜡包埋的皮下脂肪组织切片进行免疫染色,检测血管中ANP及其受体NPR-A、NPR-B和NPR-C的表达。
轻度(2.78±0.67 ng/ml,p<0.05)和重度(2.53±0.18 ng/ml,p<0.01)子痫前期患者的Corin浓度显著高于血压正常(1.58±0.08 ng/ml)和CHT(1.55±0.20 ng/ml)组。CHT(1.59±0.53 ng/ml,p<0.05)和重度子痫前期(1.42±0.24 ng/ml,p<0.01)患者的pro-ANP浓度显著高于血压正常(0.48±0.06 ng/ml)和轻度子痫前期(0.52±0.09 ng/ml)组。在血压正常和子痫前期孕妇的母体血管中未检测到ANP和NPR-B的表达,但子痫前期孕妇母体血管内皮中NPR-A表达降低,NPR-C表达增加。
ANP是一种血管舒张剂,NPR-C是ANP的清除受体。NPR-C表达上调的结果表明子痫前期循环中ANP的清除或降解增加。这些结果还提示pro-ANP/corin/NPR信号通路在子痫前期的血管系统中占主导地位。