Antihypertensive therapy responsiveness and adverse outcomes in preeclampsia: insights into molecular mechanisms underlying cardiovascular and renal complications

Abstract

IntroductionPreeclampsia (PE) is a multisystem disorder that affects 2%-8% of pregnancies worldwide and is a leading cause of maternal and fetal morbidity and mortality (Duley, 2009). PE is defined as new-onset maternal blood pressure greater than 140/90 mmHg after the 20th week of pregnancy that occurs along with proteinuria or other indications of renal insufficiency, thrombocytopenia, liver dysfunction, pulmonary edema, and cerebral disturbances (American College of Obstetricians and Gynecologists, 2013). The pathogenesis of PE is multifactorial with recognized placental, vascular, renal, and immunological contributions (Turbeville and Sasser, 2020).PE is characterized by defective placentation, abnormal spiral artery remodeling, placental ischemia, oxidative stress at the maternal-fetal interface, and angiogenic imbalance in the maternal circulation, thereby resulting in endothelial dysfunction and end-organ damage (Phipps et al., 2019). Noteworthy, several studies ratify the relationship of PE with future risk for cardiovascular disease, and accumulating evidence suggests an association of PE with long-term renal disease, although further studies on the mechanisms underlying this increased risk are needed (Turbeville and Sasser, 2020). However, significant knowledge gaps still exist in identifying the mechanisms that link placental ischemia to maternal systemic vascular and renal dysfunction (Wang et al., 2023).Current treatment strategies for PE focus on stabilizing the maternal symptoms in order to prolong pregnancy and allow additional fetal development, and managing maternal