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对非洲裔孕妇妊娠高血压疾病中促血管生成和抗血管生成因子的观察性研究。

An observational study of pro- and anti-angiogenic factors in hypertensive disorders of pregnancy in women of African ancestry.

作者信息

Soobryan Nerolen, Kumar Ajit, Moodley Jagidesa, Mackraj Irene

机构信息

Discipline of Human Physiology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.

Discipline of Microbiology, School of Life Sciences, College of Agriculture, Engineering and Science, University of KwaZulu-Natal (Westville Campus), Durban, Republic of South Africa.

出版信息

J Obstet Gynaecol. 2022 Oct;42(7):2698-2703. doi: 10.1080/01443615.2022.2099253. Epub 2022 Jul 22.

Abstract

Hypertensive disorders in pregnancy (HDPs) are the leading cause of maternal and perinatal deaths worldwide. Despite the widely reported multisystemic pathophysiology of pre-eclampsia and other HDPs, it is unknown whether these disorders represent a continuum or separate entities making clinical diagnosis a challenge. This study aimed to investigate angiogenic, metabolic and immunoregulatory specific profiles of hypertensive and gestationally matched normotensive pregnancies. A total of 200 pregnancies from a regional hospital in South Africa, via convenience sampling, were quantitatively analysed for circulating sFlt-1; PlGF; VEGF; sENG; PAPP-A; PP13; ADAMTS 12; TGF-β1 in maternal serum samples using ELISA technique. Serum protein markers TGF-β1, sENG and PAPP-A were significantly increased ( < .05) in early-onset pre-eclampsia vs. NG1 groups. sFlt-1 was significantly higher in late-onset pre-eclampsia vs NG2 groups. The GH group showed a significant increase in TGF-β1 and PAPP-A vs. NG1 counterpart. ADAMTS12 and sENG were significantly lower in gestational hypertension vs. early-onset pre-eclampsia. No significant differences were seen in PlGF, VEGF and PP13 levels across the groups. These changes show the HDP spectrum has distinct characteristics on the angiogenic profile. Based on these results, further validation of diagnostic and prognostic biomarkers of pre-eclampsia and gestational hypertension is warranted.Impact statement Hypertensive pregnancy disorders are a public health problem with adverse effects on both mother and neonate. The elusive pathogenesis of this syndrome combined with the late prevalence of symptoms leaves clinicians with a myriad of theories and indefinite treatments. The investigation into conventional anti-/angiogenic factors has been extensively studied in pre-eclampsia patients only. The overlapping clinical presentation of pre-eclampsia and gestational hypertension further complicates the diagnosis of disorders. The investigation of novel angiogenic, metabolic and inflammatory markers will firstly contribute to generating a database for researchers both nationally and internationally. This combinatory triad of markers will assist in elucidating and differentiating between early- and late-onset preeclampsia versus gestational hypertension. The results of our cohort study suggest possible early diagnostic markers for pre-eclampsia and gestational hypertension. Research in this area will contribute to an improvement in early disease management which will ultimately lead to a reduction in health care costs and mortality rate locally and globally. It will also enforce diagnostic and prognostic markers for hypertensive pregnancy diseases and warrant further investigation into the proteins primarily involved in the trophoblastic invasion. This will then clarify whether these two closely related hypertensive disorders represent a continuum or two separate entities.

摘要

妊娠期高血压疾病(HDPs)是全球孕产妇和围产儿死亡的主要原因。尽管子痫前期和其他HDPs的多系统病理生理学已被广泛报道,但尚不清楚这些疾病是代表一个连续体还是独立的实体,这使得临床诊断成为一项挑战。本研究旨在调查高血压妊娠和与之孕周匹配的正常血压妊娠的血管生成、代谢和免疫调节特异性特征。通过便利抽样,对南非一家地区医院的200例妊娠进行了研究,采用ELISA技术对孕妇血清样本中的循环sFlt-1、PlGF、VEGF、sENG、PAPP-A、PP13、ADAMTS 12、TGF-β1进行了定量分析。与NG1组相比,早发型子痫前期患者血清蛋白标志物TGF-β1、sENG和PAPP-A显著升高(P<0.05)。与NG2组相比,晚发型子痫前期患者sFlt-1显著升高。与NG1组相比,GH组TGF-β1和PAPP-A显著升高。与早发型子痫前期相比,妊娠期高血压患者ADAMTS12和sENG显著降低。各组间PlGF、VEGF和PP13水平未见显著差异。这些变化表明HDP谱在血管生成特征上具有明显特征。基于这些结果,有必要进一步验证子痫前期和妊娠期高血压的诊断和预后生物标志物。

影响声明

妊娠期高血压疾病是一个公共卫生问题,对母亲和新生儿均有不良影响。该综合征难以捉摸的发病机制加上症状出现较晚,使得临床医生有众多理论且治疗方法不明确。对传统抗血管生成/血管生成因子的研究仅在子痫前期患者中进行了广泛研究。子痫前期和妊娠期高血压重叠的临床表现进一步使疾病诊断复杂化。对新型血管生成、代谢和炎症标志物的研究首先将有助于为国内外研究人员建立一个数据库。这三种标志物的组合将有助于阐明和区分早发型和晚发型子痫前期与妊娠期高血压。我们队列研究的结果提示了子痫前期和妊娠期高血压可能的早期诊断标志物。该领域的研究将有助于改善疾病的早期管理,最终导致全球和本地医疗保健成本和死亡率的降低。它还将强化妊娠期高血压疾病的诊断和预后标志物,并促使对主要参与滋养细胞侵袭的蛋白质进行进一步研究。这将进而阐明这两种密切相关的高血压疾病是代表一个连续体还是两个独立的实体。

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