Plasminolytic Components And Their Receptors In Pathogenesis Of Preeclampsia

Abstract

Background Preeclampsia (PE) is a multisystemic pregnancy disorder affecting 2-8% of pregnancies and remains a major cause of maternal and fetal morbidity and mortality. Despite decades of research the underlying cause of preeclampsia is still not clear. The pathophysiology of preeclampsia is complex wherein the placenta plays a central role. The primary pathology appears to be at the maternal fetal interface and is characterized by poor trophoblastic invasion of the uterus. Preeclampsia is associated with failure of endovascular invasion and spiral artery remodelling and plays the central role in pathogenesis of disease. VEGF, a well-known angiogenic factor produced by placental cells, plays a central role in placental pathogenesis of PE. Annexin A2 (ANXA2) is a profibrinolytic receptor required for plasminolysis, which is an important step in the formation of new blood vessel along with VEGF.ANXA2 increases tissue plasminogen activator (tPA) mediated plasmin generation and plasminogen activator inhibitor (PAI-1) inhibit the tPA.Preeclampsia is also associated with maternal, placental aggravated inflammatory response and generalized endothelial damage AnnexinA1 (ANXA1) is glucocorticoid regulated protein regulates a wide range of cellular and molecular steps of the inflammatory response and is implicated in resolution of inflammation.Galectin-3(Gal-3), β-galcotoside-binding lectin participates in many functions, both intra- and extracellular. Recently it has been shown that galectin-3 modulates the inflammation. Role of ANXA1 and Gal-3 is poorly studied in context with human reproductive disease like PE. Therefore, the present study examined the expression of above proteins which are involved in plasminolysis, angiogenesis and modulation of inflammation and their association in the placental bed of pregnancy with and without PEObjectives a. To evaluate the alterations in gross placental morphology of PE compared to placenta of normal women. b. To demonstrate expression pattern ofANXA2, ANXA1, VEGF, tPA, PAI-1, EGFR and Gal-3 in placental tissue from women with and without Preeclampsia. c. To evaluate the correlation between expression of these downstream plasminolytic proteins at the membrane of the placental cellular component to get insight into their possible relationship to placental angiogenesis and inflammation to verify whether it has some role in the development of Preeclampsia. Material and methods The study group comprised of placental tissues procured from gestations with PE (n = 40) and without (n = 30) PE. The expression of ANXA2, ANXA1, VEGF, tPA, PAI-1, EGFR and Gal-3 in the placental villous tissue was evaluated quantitatively by means of IHC, Western blotting and RT-PCR. Results Expression analysis illustrated that significant decrease in the expression of growth proteins VEGF, EGFR and profibrinolytic receptor ANXA2 in PE group and increase expression of tPA and PAI-1 compared with the normotensive control group. Expression of inflammation modulatory proteins ANXA1 and Gal-3 in PE group was more compared with the normotensive control group (P< 0.05) Conclusion Decreased expression of ANXA2 and VEGF with increased expression of PAI-1 is mainly responsible for altered angiogenic and fibrinolytic activity inPE. The increased expression of AnxA1 and Gal-3 in placental bed may be associated with a systemic inflammatory response in PE, suggesting role of above proteins in PE pathogenesis.