Abstract-Preeclampsia is a significant cause of maternal and fetal morbidity and mortality worldwide. A clinically useful screening test that can predict development of preeclampsia at an early stage is urgently needed. The detection of podocyturia by immunohistochemistry after cell culture has been noted as a reliable marker for preeclampsia. However, this method is laborious and carries the risk of cell culture contamination. The aim of this study was to investigate the diagnostic value of quantitative polymerase chain reaction as a rapid method to detect preeclampsia. Clean-catch urine samples were collected from preeclamptic (n=35), healthy pregnant (n=34), and healthy nonpregnant (n=12) women. Furthermore, a control group of women with gestational hypertension (n=5) was included. Quantitative polymerase chain reaction analysis was performed for podocyte-specific markers. Receiver operating characteristic curve analyses were performed. Significantly elevated mRNA levels of nephrin, podocin, and vascular endothelial growth factor were detected in preeclamptic women compared with healthy pregnant and healthy nonpregnant controls. In addition, significantly elevated levels of nephrin mRNA were detected in urine of preeclamptic women compared with women with gestational hypertension. A positive correlation (ρ=0.82; P<0.0001) was observed between nephrin and vascular endothelial growth factor mRNA levels in preeclamptic women. Receiver operating characteristic curve analyses demonstrated a strong ability of this method to discriminate between the different study groups. Quantitative polymerase chain reaction analysis of podocyte-specific molecules in urine samples is a rapid and reliable method to quantify podocyturia. We demonstrate that this method distinguishes preeclamptic patients from healthy controls and women with gestational hypertension. This method may be a tool for the detection of preeclampsia at an earlier stage, thereby preventing maternal and fetal morbidity and mortality.
The presence of distinct electrophysiological pathways within the atrioventricular node (AVN) is a prerequisite for atrioventricular nodal reentrant tachycardia to occur. In this study, the different cell contributions that may account for the anatomical and functional heterogeneity of the AVN were investigated. To study the temporal development of the AVN, the expression pattern of ISL1, expressed in cardiac progenitor cells, was studied in sequential stages performing co-staining with myocardial markers (TNNI2 and NKX2-5) and HCN4 (cardiac conduction system marker). An ISL1+/TNNI2+/HCN4+ continuity between the myocardium of the sinus venosus and atrioventricular canal was identified in the region of the putative AVN, which showed a pacemaker-like phenotype based on single cell patch-clamp experiments. Furthermore, qPCR analysis showed that even during early development, different cell populations can be identified in the region of the putative AVN. Fate mapping was performed by in ovo vital dye microinjection. Embryos were harvested and analysed 24 and 48 hrs post-injection. These experiments showed incorporation of sinus venosus myocardium in the posterior region of the atrioventricular canal. The myocardium of the sinus venosus contributes to the atrioventricular canal. It is postulated that the myocardium of the sinus venosus contributes to nodal extensions or transitional cells of the AVN since these cells are located in the posterior region of the AVN. This finding may help to understand the origin of atrioventricular nodal reentrant tachycardia.
RHOA-ROCK signalling is involved in establishing the right-sided SAN as the definitive pacemaker of the heart and restricts typical pacemaker gene expression to the right side of the sinus venosus myocardium.
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