Role of HMGB۱ and decorin in preeclampsia

Preeclampsia (PE) is a common, pregnancy-specific disease that belongs to the family of “hypertensive disorders in pregnancy” and is characterized by hypertension, proteinuria and other systemic disturbances at or after ۲۰ weeks of gestation. PE is a major contributor to maternal and fetal morbidity and mortality. Eventhough the precise mechanisms of PE pathogenesis remains unknown, it is widely acknowledged that the placenta is the central organ in its pathogenesis, and PE is caused by maternal responses to abnormal placentation and associated with an increased inflammatory state. Pre-eclampsia is closely related to maternal malfunction of the vasculature and is a major cardiovascular risk for the duration of the pregnancy, post-parturition and in later life. Also, endothelial dysfunction may contribute to elevate the peripheral resistance of blood vessels, which forms an essential component of the maternal syndrome. This study is aimed at the study of sterile immunomodulatory profile of normal-pregnant versus pre-eclamptic subjects and focuses on the identification of potential biomarkers for the early detection of PE and the changes in the hemodynamic parameters leadingto the pathophysiology of PE. There have been a lack in the proper understanding of the pathophysiology of PE & hence, no effective therapy or treatment is available so far. The levels of NO were significantly decreased in PE as compared to healthy pregnant subjects. As NO is a potent vasodilator, when its level in circulation decreases, the contraction of blood vessels increases which leads to elevation in the blood pressure. In our study, we observed that there is a marked increase in the expression level of SI markers (DAMPs) such as HMGB۱, HSP۹۰, vWF and DCN in plasma as well as in the placental tissue. From these observations, we can conclude that these inflammatory markers play an important role in the commencement of the pathophysiology of PE. We observed a decreasing trend in all SI markers when the pre and post-delivery samples of PE patients were compared, however significant reduction was seen only in the case of DCN for the SI markers. Therefore, it can be deduced that the DCN is one of the most important molecules which plays a significant role in the pathophysiology as well as progression of PE. On comparing the biochemical reports of the PE and normal subjects we have found that there is statistically significant increase in the biochemical parameters of the patients versus normal subjects. We observed that certain biochemical parameters such as S. Alkaline phosphate, SGOT, SGPT and protein concentration were significantly increased in PE as compared to healthy controls while no significant change was observed in blood urea and serum creatinine levels. We also analysed the blood parameters from the CBC (complete blood count) reports of patients. On comparing both the reports we observed that the NLR (neutrophil to lymphocyte ratio) was significantly increased in PE as compared to healthy pregnant subjects. On combining all the observations, we can conclude that low levels of NO lead to placental hypoxia which induces DAMPs expression. Increased expression of DAMPs in turn acts as a stimulus for neutrophil activation in increasing the NLR in PE patients