The prediction of early preeclampsia: Results from a longitudinal proteomics study.

ObjectivesTo identify maternal plasma protein markers for early preeclampsia (delivery Study designThis longitudinal case-control study included 90 patients with a normal pregnancy and 33 patients with early preeclampsia. Two to six maternal plasma samples were collected throughout gestation from each woman. The abundance of 1,125 proteins was measured using high-affinity aptamer-based proteomic assays, and data were modeled using linear mixed-effects models. After data transformation into multiples of the mean values for gestational age, parsimonious linear discriminant analysis risk models were fit for each gestational-age interval (8-16, 16.1-22, 22.1-28, 28.1-32 weeks). Proteomic profiles of early preeclampsia cases were also compared to those of a combined set of controls and late preeclampsia cases (n = 76) reported previously. Prediction performance was estimated via bootstrap.ResultsWe found that 1) multi-protein models at 16.1-22 weeks of gestation predicted early preeclampsia with a sensitivity of 71% at a false-positive rate (FPR) of 10%. High abundance of matrix metalloproteinase-7 and glycoprotein IIbIIIa complex were the most reliable predictors at this gestational age; 2) at 22.1-28 weeks of gestation, lower abundance of placental growth factor (PlGF) and vascular endothelial growth factor A, isoform 121 (VEGF-121), as well as elevated sialic acid binding immunoglobulin-like lectin 6 (siglec-6) and activin-A, were the best predictors of the subsequent development of early preeclampsia (81% sensitivity, FPR = 10%); 3) at 28.1-32 weeks of gestation, the sensitivity of multi-protein models was 85% (FPR = 10%) with the best predictors being activated leukocyte cell adhesion molecule, siglec-6, and VEGF-121; 4) the increase in siglec-6, activin-A, and VEGF-121 at 22.1-28 weeks of gestation differentiated women who subsequently developed early preeclampsia from those who had a normal pregnancy or developed late preeclampsia (sensitivity 77%, FPR = 10%); 5) the sensitivity of risk models was higher for early preeclampsia with placental MVM lesions than for the entire early preeclampsia group (90% versus 71% at 16.1-22 weeks; 87% versus 81% at 22.1-28 weeks; and 90% versus 85% at 28.1-32 weeks, all FPR = 10%); and 6) the sensitivity of prediction models was higher for severe early preeclampsia than for the entire early preeclampsia group (84% versus 71% at 16.1-22 weeks).ConclusionWe have presented herein a catalogue of proteome changes in maternal plasma proteome that precede the diagnosis of preeclampsia and can distinguish among early and late phenotypes. The sensitivity of maternal plasma protein models for early preeclampsia is higher in women with underlying vascular placental disease and in those with a severe phenotype

“Single–Single” Amphiphilic Janus Dendrimers Self-Assemble into Uniform Dendrimersomes with Predictable Size

An accelerated modular synthesis of six libraries containing 29 amphiphilic Janus dendrimers, employed to discover and predict functions <i>via</i> primary structures, is reported. These dendrimers were constructed from a single hydrophobic and a single hydrophilic dendron, interconnected with l-Ala to form two constitutional isomeric libraries, with Gly to produce one library, and with l-propanediol ester to generate two additional constitutional isomeric libraries. They are denoted “single–single” amphiphilic Janus dendrimers. Assemblies obtained by injection of their ethanol solution into water were analyzed by dynamic light scattering and cryogenic transmission electron microscopy. A diversity of complex structures including soft and hard dendrimersomes, cubosomes, solid lamellae, and rod-like micelles were obtained in water. It was discovered that the “single–single” amphiphilic Janus dendrimers containing three triethylene glycol groups in the hydrophilic dendron favored the formation of dendrimersomes. Assemblies in bulk analyzed by differential scanning calorimetry and powder X-ray diffraction revealed that the amphiphilic Janus dendrimers with melting point or glass transition below room temperature self-assemble into soft dendrimersomes in water, while those with higher temperature transitions produce hard assemblies. In the range of concentrations where their size distribution is narrow, the diameter of the dendrimersomes is predictable by the <i>d</i>-spacing of their assemblies in bulk. These results suggested the synthesis of Library 6 containing two simpler constitutional isomeric benzyl ester based amphiphilic Janus dendrimers that self-assemble in water into soft dendrimersomes and multidendrimersome dendrimersomes with predictable dimensions