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Differential impact of prostaglandin H synthase 1 knockdown on platelets and parturition.
- Source :
-
Journal of Clinical Investigation . Apr2005, Vol. 115 Issue 4, p986-995. 10p. 1 Color Photograph, 1 Black and White Photograph, 1 Chart, 7 Graphs. - Publication Year :
- 2005
-
Abstract
- Platelet activation is a hallmark of severe preeclampsia, and platelet PGH synthase 1-derived (PGHS1-derived) thromboxane A(2) (TxA(2)) has been implicated in its pathogenesis. However, genetic disruption of PGHS1 delays parturition. We created hypomorphic PGHS1 (PGHS1(Neo/Neo)) mice, in which the substantial but tissue-dependent variability in the inhibition of PGHS1-derived eicosanoids achieved by low-dose aspirin treatment is mimicked, to assess the relative impact of this strategy on hemostatic and reproductive function. Depression of platelet TxA(2) by 98% in PGHS1(Neo/Neo) mice decreased platelet aggregation and prevented thrombosis. Similarly, depression of macrophage PGE(2) by 75% was associated with selectively impaired inflammatory responses. PGF(2alpha) at 8% WT levels was sufficient to induce coordinated temporal oxytocin receptor (OTR) expression in uterus and normal ovarian luteolysis in PGHS1(Neo/Neo) mice at late gestation, while absence of PGHS1 expression in null mice delayed OTR induction and the programmed decrease of serum progesterone during parturition. Thus, extensive but tissue-dependent variability in PG suppression, as occurs with low-dose aspirin treatment, prevents thrombosis and impairs the inflammatory response but sustains parturition. PGHS1(Neo/Neo) mice provide a model of low-dose aspirin therapy that elucidates how prevention or delay of preeclampsia might be achieved without compromising reproductive function. [ABSTRACT FROM AUTHOR]
- Subjects :
- *PROSTAGLANDINS
*BLOOD platelets
*PARTURITION
*ENZYMES
*ASPIRIN
*PROGESTERONE
*ANIMAL experimentation
*ARACHIDONIC acid
*CELL receptors
*COMPARATIVE studies
*EDEMA
*ESTRADIOL
*LABOR (Obstetrics)
*RESEARCH methodology
*MEDICAL cooperation
*MEMBRANE proteins
*MICE
*OVARIES
*OXIDOREDUCTASES
*PREECLAMPSIA
*RESEARCH
*RESEARCH funding
*THROMBOXANES
*UTERUS
*EVALUATION research
Subjects
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 115
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- 16624346
- Full Text :
- https://doi.org/10.1172/JCI200523683