Department of Cardiology, Boston Children's Hospital, Harvard Medical School, Boston, MA (A.M.V.)Circulation (Impact Factor: 14.43). 10/2013; 128(17):e344-5. DOI: 10.1161/CIRCULATIONAHA.113.003858
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ABSTRACT: Unlabelled: Epidemiological studies suggest that the impact of preeclampsia does not only affect the mother but also the children. We know that adverse events in utero may predispose individuals to premature cardiovascular disease in adulthood, but we do not know the mechanisms. To gain insights into the mechanisms of cardiovascular dysfunction in the offspring of preeclampsia, we employed a global stable isotope labeled profiling strategy using iTRAQ reagents, followed by 2D-LC-MS/MS. We identified 1521 non-redundant proteins, and 1496 of these were quantified. Further analysis identified 53 differentially expressed proteins in umbilical artery; 22 proteins were up-regulated and 31 proteins were down-regulated. K-means clustering analysis showed that there was a specific protein expression profile in the umbilical artery which could distinguish between normal and preeclampsia patients. These 53 proteins were analyzed by Ingenuity Pathway Analysis (IPA) and were found to play important roles in the angiogenesis, vasculogenesis, and development of the cardiovascular system. In addition, the differential expression of three cardiovascular relative proteins (aldose reductase, fibronectin-1, fibrillin-1) was independently verified using western blot. These results may supply new insights into the mechanisms of vascular dysfunction in the offspring of preeclampsia patients. Biological significance: Increasing evidence suggests that the children who were exposed to preeclampsia in utero have an increased cardiovascular risk, and vascular dysfunction has been found in some children born of preeclampsia. However, the mechanism remains largely unknown. In this study, we identified 1521 non-redundant proteins, and 1496 of these were quantified. Further analysis identified 53 differentially expressed proteins in the umbilical artery from preeclampsia patients; 22 proteins were up-regulated and 31 proteins were down-regulated. Some of these differentially expressed proteins have been shown to play important roles in cardiovascular system development. Our results provide new insights into the potential mechanisms underlying the changed blood pressure of offspring of mothers with preeclampsia, and, the elevation of their risk of cardiovascular abnormality in later life.
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ABSTRACT: Introduction This study is to investigate the distribution of inhibitory and activating killer immunoglobulin like receptors (KIRs) and the combination of KIR/HLA-C in women with preeclampsia in the Chinese Han population compared with the control. Methods 271 patients with preeclampsia were enrolled in this study. The PCR sequence-specific primers (SSP) method was used to detect the inhibitory/activating KIRs and the HLA-C gene polymorphism. Results Our result showed that decreased numbers of individual activating KIR genes (2DS2, 2DS3, 2DS5) was observed in patients with preeclampsia and the gene frequency of total KIRs was also lower in patients compared to that of the control subjects (P =0.03). The frequency of KIR2DL1 gene was increased in the mother with preeclampsia when the fetus has a HLA-C2 alleles. Conclusion The results suggest that a genetic variation at the KIR locus might influence the susceptibility to preeclampsia in the Chinese Han population. Lacking of activating KIRs could potentially lower the uNK cell activation, thereby contributing to pathogenesis of preeclampsia. Moreover, the matching of the inhibitory or activating KIRs/HLA combination at the maternal-fetal interface seems to play a regulatory role in the occurrence of preeclampsia.