GRK2 Levels in Umbilical Arteries of Pregnancies Complicated by Gestational Hypertension and Preeclampsia

Hypertension is reported to complicate about 7–13% of all pregnancies and it represents the most common medical disorder of pregnancy.1 Preeclampsia (PE) affects 2–5% of pregnancies in developed countries2 and is a major cause of maternal and perinatal morbidity and mortality, accounting a 0.7 maternal deaths per 100,000 live births.3 This syndrome is thought to be a consequence of abnormalities in the maternal vessels supplying the placenta, leading to poor placental perfusion and release of factors causing widespread endothelial dysfunction with multiorgan system clinical features.4 The clinical findings of PE can therefore manifest, as either a maternal syndrome (hypertension and proteinuria with or without other multisystem abnormalities), or fetal syndrome as fetal growth restriction (FGR).5 This latter, though, is not exclusively observed in gestational hypertension (GH) or PE, and can be a complication of normotensive pregnancies. Although the causes of PE are unknown, the origin of the condition is recognized as lying in the placenta. Shallow endovascular cytotrophoblast invasion in the spiral arteries and endothelial cell dysfunction are two key features in the pathogenesis of PE.6 Placental ischemia is thought to develop as a result of this abnormal cytotrophoblastic invasion; this has been proposed as leading to release of placental factors and imbalance of angiogenic factors, causing the widespread endothelial dysfunction.4,7–9 G-Protein coupled receptor (GPCR) kinase 2 (GRK2) represents an important regulator of cell functions by means of phosphorylative events on activated GPCR leading to desensitization.10 GRK2 was first identified for its ability to phosphorylate and mediate desensitization of βAR, and its transgenic overexpression causes βAR desensitization and impaired βAR mediated increase in cardiac contractility. Recently, its ability to recognize and phosphorylate many more substrates has been 1Department of Obstetrics and Gynecology, Prenatal Diagnosis and high risk Pregnancy Unit, University of Naples, Federico II, Naples, Italy; 2Department of clinical medicine, cardiovascular and Immunological Sciences, University of Naples, Federico II, Naples, Italy; 3School of medicine, University of Salerno, Salerno, Italy. correspondence: Guido Iaccarino (giaccarino@unisa.it)