胎盘内源性大麻素系统:关注先兆子痫和大麻使用。

IF 6.9 1区 医学 Q1 PERIPHERAL VASCULAR DISEASE
Madhavi S Harhangi,Sinno H P Simons,Hilmar H Bijma,Anna Nguyen,Tuong-Vi Nguyen,Tu'uhevaha Kaitu'u-Lino,Irwin K M Reiss,A H Jan Danser,Michelle Broekhuizen
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引用次数: 0

摘要

背景:内源性大麻素系统(ECS)在怀孕早期起着重要作用,而怀孕期间使用大麻会增加子痫前期的风险。本研究量化了孕龄匹配的健康孕妇、先兆子痫妇女和妊娠期间使用大麻的妇女胎盘ECS组分mRNA水平。接下来,比较内源性ECS激动剂anandamide和2-花生四烯醇甘油与大麻素受体1型和2型激动剂HU-210和HU-308在绒毛膜板动脉中的作用。方法采用定量聚合酶链反应法测定胎盘mRNA水平。血管反应性研究有和没有选择性大麻素受体1型和2型拮抗剂。结果大麻使用者子痫前期负责2-花生四烯醇生成的1,2-二酰基甘油脂肪酶α的smrna水平降低,而大麻酰胺合成酶n -酰基磷脂酰乙醇胺特异性磷脂酶D的mRNA水平上调。大麻酰胺通过大麻素受体1型和2型介导健康妊娠期的松弛,而2-花生四烯醇甘油通过大麻素受体1型介导健康妊娠期的松弛。在子痫前期,阿南达胺和2-花生四烯醇甘油的作用没有改变,但不再涉及大麻素受体,而在大麻使用者中,它们的作用不存在。HU-210和HU-308放松了健康的血管,但不影响子痫前期的血管。一氧化氮供体硝普钠同样放松健康和子痫前期血管,而其在大麻使用者中的作用则大大降低。结论:在子痫前期,ECS受到干扰,内源性ECS激动剂在大麻使用者中失去扩张能力,同时这种使用也减少了NO信号。这些数据提供了反对怀孕期间使用大麻的机械证据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Placental Endocannabinoid System: Focus on Preeclampsia and Cannabis Use.
BACKGROUND The endocannabinoid system (ECS) plays an important role in the early stages of pregnancy, while cannabis use during pregnancy associates with a greater risk of preeclampsia. This study quantified the placental ECS component mRNA levels in gestational age-matched healthy pregnant women, women with preeclampsia, and women who used cannabis throughout their pregnancy. Next, it compared the effects of the endogenous ECS agonists anandamide and 2-arachidonoylglycerol with those of the cannabinoid receptor type 1 and 2 agonists HU-210 and HU-308 in chorionic plate arteries. METHODS Placental mRNA levels were quantified by quantitative polymerase chain reaction. Vascular reactivity was studied with and without selective cannabinoid receptor type 1 and 2 antagonists. RESULTS mRNA levels of 1,2-diacylglycerol lipase α, responsible for 2-arachidonoylglycerol generation, were lowered in preeclampsia, while mRNA levels of the anandamide-synthesizing enzyme N-acyl phosphatidylethanolamine-specific phospholipase D were upregulated in cannabis users. Anandamide-induced relaxation in healthy pregnancy was mediated via cannabinoid receptors type 1 and 2, while 2-arachidonoylglycerol induced relaxation via cannabinoid receptor type 1. In preeclampsia, the effects of anandamide and 2-arachidonoylglycerol were unaltered but no longer involved cannabinoid receptors, while in cannabis users their effects were absent. HU-210 and HU-308 relaxed healthy, but not preeclamptic vessels. The NO donor sodium nitroprusside similarly relaxed healthy and preeclamptic vessels, while its effects in cannabis users were greatly reduced. CONCLUSIONS The ECS is disturbed in preeclampsia, and endogenous ECS agonists lose their capacity to dilate in cannabis users, while such use also diminishes NO signaling. These data provide mechanistic evidence against cannabis use during pregnancy.
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来源期刊
Hypertension
Hypertension 医学-外周血管病
CiteScore
15.90
自引率
4.80%
发文量
1006
审稿时长
1 months
期刊介绍: Hypertension presents top-tier articles on high blood pressure in each monthly release. These articles delve into basic science, clinical treatment, and prevention of hypertension and associated cardiovascular, metabolic, and renal conditions. Renowned for their lasting significance, these papers contribute to advancing our understanding and management of hypertension-related issues.
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