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

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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.