期刊
REPRODUCTIVE SCIENCES
卷 16, 期 2, 页码 162-170出版社
SPRINGER HEIDELBERG
DOI: 10.1177/1933719108325758
关键词
Tissue factor; endometrium; hemostasis; angiogenesis; bleeding
资金
- NHLBI NIH HHS [R01 HL070004-04, R01 HL070004-01A1, R01 HL070004, R01 HL070004-03, R01 HL070004-02, 1 R01 HL070004-04] Funding Source: Medline
- NICHD NIH HHS [2 R01 HD33937-05, R01 HD033937, R01 HD033937-05] Funding Source: Medline
Factor VII binds trans-membrane tissue factor to initiate hemostasis by forming thrombin. Tissue factor expression is enhanced in decidualized human endometrial stromal cells during the luteal phase. Long-term progestin only contraceptives elicit: 1) abnormal uterine bleeding from fragile vessels at focal bleeding sites, 2) paradoxically high tissue factor expression at bleeding sites; 3) reduced endometrial blood flow promoting local hypoxia and enhancing reactive oxygen species levels; 4) aberrant angiogenesis reflecting increased stromal cell-expressed vascular endothelial growth factor, decreased Angiopoietin-1 and increased endothelial cell-expressed Angiopoietin-2. Aberrantly high local vascular permeability enhances circulating factor VII to decidualized stromal cell-expressed tissue factor to generate excess thrombin. Hypoxia-thrombin interaction augment expression of vascular endothelial growth factor and interleukin-8 by stromal cells. Thrombin vascular endothelial growth factor and interlerukin-8 synergistically augment angiogenesis in a milieu of reactive oxygen species-induced endothelial cell activation. The resulting enhanced vessel fragility promotes abnormal uterine bleeding.
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