Evidence for alpha-1-antitrypsin (A1AT) polymerization in preeclampsia: A novel mechanism for endothelial cell injury

Abstract

PREECLAMPSIA: A NOVEL MECHANISM FOR ENDOTHELIAL CELL INJURY IRINA BUHIMSCHI, GUOMAO ZHAO, GEORGE SAADE, CATALIN S. BUHIMSCHI, Yale University, Obstetrics/Gynecology, New Haven, Connecticut, Yale University, Ob./Gyn.R p=0.009], despite a significant increase its urinary excretion (O500 fold in sPE, p!0.001). In addition, urine and serum from women with sPE contained multiple immunoreactive forms of A1AT, with molecular masses both below (fragments) and above the 52 kDa mass of the monomeric A1AT (polymers). In the placenta, monomeric A1AT localized largely intravascular and to villous macrophages and syncytiotrophoblasts. The staining was significantly more evident in sPE compared with CTR. In all sPE cases, but in none of the CRLs, an intense ZA1AT staining was localized exclusively to the vascular endothelium. CONCLUSION: A1AT protein expression is increased in preeclamptic placentas. This is the first demonstration that polymerized A1AT is present in serum and urine of patients with preeclampsia, and that this material is bound to placental vascular endothelium. This suggests that the polymerized A1AT may play a role in the pathogenesis of endothelial damage in preeclampsia.