Novel regulation of human myometrial contractility by histone deacetylase 8 (HDAC8)

大约有6-10%的人类怀孕在分娩前结束。足月？而早产儿则会长期受到身体和智力障碍的困扰。此外，高达65%的围产期分娩与早产有关。迄今为止，用于停止宫缩的药物，称为宫缩抑制剂，仍然不够有效和安全，并对母亲和婴儿造成非特异性和往往危险的副作用。最近对血管平滑肌细胞的研究表明，一种特定的蛋白质组蛋白去乙酰化酶8（HDAC 8）是平滑肌的特异性标志物，对这种肌肉细胞类型的收缩性至关重要。我们的初步数据还表明，这种蛋白质可能在调节妊娠和分娩期间的子宫平滑肌活动中发挥重要作用。因此，该研究提案的目的是确定情况是否如此，并确定高选择性HDAC 8抑制剂是否可以作为潜在的新型治疗药物，更好地管理早产。

Approximately 6-10% of human pregnancies end with delivery before ?full term?, and premature born babies suffer from long term physical and mental handicap. Furthermore, up to 65% of perinatal births are related to premature birth. To date, drugs used to stop contractions, termed tocolytics, are still not effective and safe enough and cause non-specific and often dangerous side effects for both mother and infant. Recent investigations on vascular smooth muscle cells has indicated that a specific protein histone deacetylase 8 (HDAC8) is a specific marker of smooth muscle and is essential for the contractility of this muscle cell type. Our initial data also indicates that this protein may play an important role in regulating uterine smooth muscle activity during pregnancy and labour. Consequently the purpose of the research proposal are to define whether this is the case and to determine whether highly selective HDAC8 inhibitors can act as potential novel therapeutic agents in the better management of premature labour.