Development of methods for prevention and treatment of hypertension disorder of pregnancy

Abstract

Due to advancements in our elucidation of the pathogenesis and pathology of hypertension disorder of pregnancy (HDP), we now understand that the disease develops in two stages. In the first stage, placental hypoxia and ischemia occur due to failure of the vascular wall, and the muscle elastic membrane of the spiral artery is replaced by trophoblasts in the placental bed (i.e., remodeling of the spiral artery) in the course of a normal pregnancy early in gestation. This hypoxia and ischemia enhances choriocyte production of anti-angiogenesis factors like soluble Flt-1 and soluble endoglin. In the second stage, this causes vascular endothelial damage in the maternal body and the placenta, leading to the development of HDP.

Thus far, no treatment has been available to address HDP in patients, and the only course of action has been careful monitoring and consideration of the maternal body and fetus, particularly toward the end of the gestation period. However, in recent years, reports have emerged on the treatment and prevention of HDP, involving Pravastatin, Aspirin and PDE-5 inhibitors, among others. Currently, we may be at a branching point between prevention and treatment of HDP. Elucidation of the two-stage pathogenesis as described previously has contributed greatly to the development of the new treatment.

When severe, HDP can cause damage to important organs such as the kidneys, liver and brain, and thus endangers the life of the mother. In addition, since pregnancy itself is the cause of HDP, the arrival of the end of the pregnancy is the only curative treatment for it; that said, if HDP becomes severe when the fetus is still premature, management of this condition becomes very difficult. For this reason, developing methods of intervention to prevent and treat HDP onset would not only save the mother, but also improve substantially the fetal prognosis.

In conjunction with other attempts worldwide to address this matter, we feel that Japan should also establish clinical trials and conduct basic research pertaining to this condition. To this end, we propose the theme of “Development of methods for prevention and treatment of hypertension disorder of pregnancy.”