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Differential proteomic analysis of umbilical artery tissue from preeclampsia patients, using iTRAQ isobaric tags and
Hai-Tao Pan1, Meng-Xi Guo1, Yi-Meng Xiong2
1The Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China; Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, China.
Insights
Preeclampsia exposure in utero may lead to cardiovascular issues in children. This study identified 53 key proteins in umbilical arteries, revealing mechanisms behind offspring vascular dysfunction and future cardiovascular risk.
Area of Science:
- Proteomics
- Cardiovascular Biology
- Developmental Biology
Background:
- Preeclampsia impacts maternal and child health, potentially predisposing offspring to adult cardiovascular disease.
- Mechanisms linking in utero preeclampsia exposure to offspring cardiovascular dysfunction remain largely unknown.
Purpose of the Study:
- To investigate the molecular mechanisms of cardiovascular dysfunction in offspring exposed to preeclampsia in utero.
- To identify protein expression profiles in umbilical arteries associated with preeclampsia.
Main Methods:
- Utilized iTRAQ reagents and 2D-LC-MS/MS for global proteomic profiling of umbilical artery samples.
- Identified and quantified non-redundant proteins, with subsequent analysis of differentially expressed proteins.
- Verified differential expression of selected cardiovascular proteins using Western blot.
Main Results:
- Identified 1521 non-redundant proteins, quantifying 1496.
- Discovered 53 differentially expressed proteins in umbilical arteries of preeclampsia patients (22 up-regulated, 31 down-regulated).
- K-means clustering revealed distinct protein profiles differentiating normal and preeclampsia umbilical arteries; pathway analysis implicated these proteins in cardiovascular development.
Conclusions:
- The identified 53 differentially expressed proteins offer insights into mechanisms of vascular dysfunction in preeclampsia offspring.
- Findings suggest potential links between altered umbilical artery protein expression and later-life cardiovascular abnormalities in offspring.
- This research provides a foundation for understanding preeclampsia's long-term cardiovascular impact on children.
Abstract:
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.
