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首页> 外文期刊>American Journal of Physiology >Placental growth factor reverses decreased vascular and uteroplacental MMP-2 and MMP-9 and increased MMP-1 and MMP-7 and collagen types I and IV in hypertensive pregnancy
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Placental growth factor reverses decreased vascular and uteroplacental MMP-2 and MMP-9 and increased MMP-1 and MMP-7 and collagen types I and IV in hypertensive pregnancy

机译：胎盘生长因子逆转血管和子属MMP-2和MMP-9和MMP-1和MMP-7和胶原蛋白类型和IV中的血管妊娠中的MMP-1和MMP-7增加

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摘要

Preeclampsia is a complication of pregnancy manifested as maternal hypertension (HTN) and fetal intrauterine growth restriction, with unclear mechanisms. Placental ischemia increases antiangiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) relative to angiogenic placental growth factor (PlGF); however, the molecular targets are unclear. To test the hypothesis that placental ischemia-induced changes in sFlt-1 and PlGF target vascular and uteroplacental matrix metalloproteinases (MMPs), we tested whether raising the sFlt-1-to-PlGF ratio by infusing sFlt-1 (10 μg·kg?1·day?1) in pregnant (Preg) rats increases blood pressure (BP) and alters MMPs and whether correcting sFlt-1/PlGF by infusing PlGF (20 μg·kg?1·day?1) in Preg rats with reduced uterine perfusion pressure (RUPP) improves BP and reverses the changes in MMPs. On gestational day 19, BP was higher and the litter size and uterine, placenta, and pup weight were less in Preg + sFlt-1 and RUPP than Preg rats and restored in RUPP + PlGF versus RUPP rats. Gelatin and casein zymography and Western blots revealed decreases in MMP-2 and MMP-9 and increases in MMP-1 and MMP-7 in the aorta, uterine artery, uterus, and placenta of Preg + sFlt-1 and RUPP versus Preg rats, which were reversed in RUPP + PlGF versus RUPP rats. Collagen types I and IV were more abundant in Preg + sFlt-1 and RUPP versus Preg rats and were reversed in RUPP + PlGF versus RUPP rats. Thus, PlGF reverses decreased vascular and uteroplacental MMP-2 and MMP-9 and increased MMP-1, MMP-7, and collagen types I and IV induced by placental ischemia and sFlt-1 in HTN in pregnancy. Angiogenic factors and MMP modulators could rectify changes in MMPs and collagen, restore vascular and uteroplacental remodeling, and improve HTN and intrauterine growth restriction in preeclampsia.NEW & NOTEWORTHY Understanding the mechanisms of preeclampsia could help in its prevention and management. This study shows that correcting soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) imbalance by infusing PlGF reverses the decreases in vascular and uteroplacental matrix metalloproteinase (MMP)-2 and MMP-9 and the increases in MMP-1, MMP-7, and collagen types I and IV induced by placental ischemia and antiangiogenic sFlt-1 in hypertension in pregnancy. Angiogenic factors and MMP modulators could rectify changes in vascular and uteroplacental MMPs and collagen content and ameliorate hypertension and intrauterine growth restriction in preeclampsia.
机译：预口度是妊娠的并发症表现为母体高血压（HTN）和胎儿宫内生长限制，机制不明确。胎盘缺血相对于血管生成胎盘生长因子（PLGF）增加抗血管生成可溶性FMS样酪氨酸激酶-1（SFLT-1）;然而，分子靶标尚不清楚。为了测试胎盘性缺血诱导的SFLT-1和PLGF靶血管和子属化族基质金属蛋白酶（MMP）的假设，我们测试了是否通过输注SFLT-1来提高SFLT-1-PLGF比（10μg·kg？怀孕（PREG）大鼠的1·日？灌注压力（RUPP）改善了BP并逆转了MMP的变化。在妊娠第19天，BP较高，PREG + SFLT-1和RUPP的垃圾尺寸和子宫，胎盘和幼崽体重少于PREG大鼠，并在Rupp + PLGF与Rupp大鼠中恢复。明胶和酪蛋白谱和蛋白质印迹显示在MMP-2和MMP-9中的降低，并且在AORTA，子宫动脉，子宫和PREG + SFLT-1和RUPP与PREG大鼠的胎盘中增加MMP-1和MMP-7，在Rupp + PLGF与Rupp大鼠中逆转。 PREG + SFLT-1和RUPP与PREG大鼠的胶原蛋白类型I和IV更丰富，并在Rupp + PLGF与Rupp大鼠中逆转。因此，PLGF反转降低血管和子宫内科医生MMP-2和MMP-1，MMP-1，MMP-7和妊娠中HTN中的SFLT-1诱导的MMP-1，MMP-7和胶原蛋白类型I和IV型。血管生成因子和MMP调节剂可以整流MMP和胶原蛋白的变化，恢复血管和子属改造，并改善Preclampsia中的HTN和宫内生长限制.New和值得注意的了解预防坦克西亚的机制可以有助于预防和管理。本研究表明，通过输注PLGF校正可溶性FMS样酪氨酸激酶-1（SFLT-1）/胎盘生长因子（PLGF）不平衡反转血管和子宫内膜基质金属蛋白酶（MMP）-2和MMP-9的降低以及增加在妊娠期高血压高血压中胎盘缺血和抗血管生成SFLT-1诱导的MMP-1，MMP-7和IV型和IV型。血管生成因子和MMP调节剂可以整流血管和子叶病毒和胶原蛋白含量的变化，并改善先兆子痫的高血压和宫内生长限制。

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