Angiogenic Dysregulation in Pregnancy-Related Hypertension-A Role for Metformin.

Abstract

In the face of escalating maternal and fetal health threats, hypertensive pregnancy disorders (HPDs) is one of the leading cause of maternal and fetal morbidity and mortality. The range of HPDs include white-coat hypertension, chronic hypertension, gestational hypertension, mild-to-moderate and severe preeclampsia and eclampsia. Current evidence implicates an imbalance of circulating anti- and angiogenic factors in HPDs emanating from the placental vasculature, impacting on angiogenesis. Delivery of the fetus is thus far the only curative measure, albeit with increased risk. Resultant endothelial dysfunction caused by the excessive production of placental soluble fms-like tyrosine kinase-1 has been the basis of many studies to find a safer treatment strategy. Metformin, used historically in the treatment of diabetes mellitus has also found its therapeutic reach in many other disease states. These include, but are not limited to, improving blood flow in certain cancer types, treatment of polycystic ovarian disease, improving vasodilation, and reducing inflammation. Metformin is used to treat hyperglycemic endothelial dysfunction through the enhancement of the nitric oxide system, endothelin-derived hyperpolarizing factor and sirtuin 1. Similarly, endothelial dysfunction in preeclampsia and other HPDs leads to a hypoxic state and elevated blood pressures. Dubbed as the new "aspirin" of current times, the retardation of the antiangiogenic status by metformin provides an exciting and promising alternate strategy in treating these pregnancy disorders.