Razak Azlina A, Leach Lopa, Ralevic Vera
1 School of Life Sciences, University of Nottingham, Medical School, Queen's Medical Centre, Nottingham, UK.
2 Faculty of Medicine & Health Sciences, UCSI University, Kuala Lumpur, Malaysia.
Diab Vasc Dis Res. 2018 Nov;15(6):528-540. doi: 10.1177/1479164118790904. Epub 2018 Aug 22.
There is clinical and experimental evidence for altered adenosine signalling in the fetoplacental circulation in pregnancies complicated by diabetes, leading to adenosine accumulation in the placenta. However, the consequence for fetoplacental vasocontractility is unclear. This study examined contractility to adenosine of chorionic vessels from type 1 diabetes mellitus, gestational diabetes mellitus and normal pregnancies.
Chorionic arteries and veins were isolated from human placenta from normal, gestational diabetes mellitus and type 1 diabetes mellitus pregnancies. Isometric tension recording measured responses to adenosine and the thromboxane A analogue U46619 (thromboxane A mediates fetoplacental vasoconstriction to adenosine). Adenosine and thromboxane prostanoid receptor protein expression was determined by immunoblotting.
Adenosine elicited contractions in chorionic arteries and veins which were impaired in both gestational diabetes mellitus and type 1 diabetes mellitus. Contractions to potassium chloride were unchanged. Adenosine A and A receptor protein levels were not different in gestational diabetes mellitus and normal pregnancies. Contractions to U46619 were unaltered in gestational diabetes mellitus arteries and increased in type 1 diabetes mellitus arteries. Overnight storage of vessels restored contractility to adenosine in gestational diabetes mellitus arteries and normalized contraction to U46619 in type 1 diabetes mellitus arteries.
These data are consistent with the concept of aberrant adenosine signalling in diabetes; they show for the first time that this involves impaired adenosine contractility of the fetoplacental vasculature.
有临床和实验证据表明，在患有糖尿病的妊娠中，胎儿 - 胎盘循环中的腺苷信号传导发生改变，导致胎盘内腺苷积累。然而，其对胎儿 - 胎盘血管收缩性的影响尚不清楚。本研究检测了1型糖尿病、妊娠期糖尿病和正常妊娠的绒毛血管对腺苷的收缩性。
从正常妊娠、妊娠期糖尿病和1型糖尿病妊娠的人胎盘中分离出绒毛动脉和静脉。通过等长张力记录来测量对腺苷和血栓素A类似物U46619（血栓素A介导胎儿 - 胎盘血管对腺苷的收缩）的反应。通过免疫印迹法测定腺苷和血栓素前列腺素受体蛋白的表达。
腺苷在绒毛动脉和静脉中引起收缩，在妊娠期糖尿病和1型糖尿病中这种收缩均受损。对氯化钾的收缩反应未改变。妊娠期糖尿病和正常妊娠中腺苷A1和A2受体蛋白水平无差异。妊娠期糖尿病动脉对U46619的收缩反应未改变，而1型糖尿病动脉中对U46619的收缩反应增加。血管过夜储存恢复了妊娠期糖尿病动脉对腺苷的收缩性，并使1型糖尿病动脉中对U46619的收缩反应正常化。
这些数据与糖尿病中腺苷信号异常的概念一致；它们首次表明这涉及胎儿 - 胎盘血管系统中腺苷收缩性受损。
