Angiogenic defects in preeclampsia: What is known, and how are such defects relevant to preeclampsia pathogenesis?

Preeclampsia is a devastating pregnancy-associated hypertensive syndrome. Although it is quite common, the pathophysiology of preeclampsia is not yet clear and remains "a disease of theory". Angiogenic defect hypotheses have been intensively investigated, and some biomarkers have been independently analyzed as pathogenic clinical target molecules without direct proof of their roles in preeclampsia. In this review, we assessed an up-to-date list of proposed angiogenic defects for their relevance to preeclampsia. In addition, we introduce our working hypothesis of preeclampsia pathophysiology, which involves interactions between metabolic and angiogenic defects.