Involvement of human decidual cell-expressed tissue factor in uterine hemostasis and abruption.
Vascular injury increases access and binding of plasma-derived factor VII to perivascular cell membrane-bound tissue factor (TF). The resulting TF/VIIa complex promotes hemostasis by cleaving pro-thrombin to thrombin leading to the fibrin clot. In human pregnancy, decidual cell-expressed TF prevents decidual hemorrhage (abruption). During placentation, trophoblasts remodel decidual spiral arteries into high conductance vessels. Shallow trophoblast invasion impedes decidual vascular conversion, producing an inadequate uteroplacental blood flow that elicits abruption-related placental ischemia. Thrombin induces several biological effects via cell surface protease activated receptors. In first trimester human DCs thrombin increases synthesis of sFlt-1, which elicits placental ischemia by impeding angiogenesis-related decidual vascular remodeling. During pregnacy, the fibrillar collagen-rich amnion and choriodecidua extracellular matrix (ECM) provides greater than additive tensile strength and structural integrity. Thrombin acts as an autocrine/paracrine mediator that degrades these ECMs by augmenting decidual cell expression of: 1) matrix metalloproteinases and 2) interleukin-8, a key mediator of abruption-associated decidual infiltration of neutrophils, which express several ECM degrading proteases. Among the cell types at the maternal fetal interface at term, TF expression is highest in decidual cells indicating that this TF meets the hemostatic demands of labor and delivery. TF expression in cultured term decidual cells is enhanced by progestin and thrombin suggesting that the maintenance of elevated circulating progesterone provides hemostatic protection and that abruption-generated thrombin acts in an autocrine/paracrine fashion on decidual cells to promote hemostasis via enhanced TF expression.
Lockwood
C J
CJ
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06520, USA.
Paidas
M
M
Murk
W K
WK
Kayisli
U A
UA
Gopinath
A
A
Huang
S J
SJ
Krikun
G
G
Schatz
F
F
D000037:Abruptio Placentae / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D003656:Decidua / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006487:Hemostasis; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism*; D014592:Uterine Hemorrhage / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D014599:Uterus / Q000098:blood supply* / Q000378:metabolism
D013925:Thromboplastin; D013917:Thrombin