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Thrombin in Pregnancy and Preeclampsia: Expression, Localization, and Vasoactivity in Brain and Microvessels From
Olivia M O'Brien1,2, Sarah M Tremble2, Ari Kropf2
1Department of Electrical and Biomedical Engineering, University of Vermont College of Engineering and Mathematical Sciences, Burlington, VT.
Journal of Cardiovascular Pharmacology
|June 26, 2024
Summary
Thrombin, a clotting factor, impacts brain arterioles in pregnancy and preeclampsia. Its expression and effects in the brain suggest roles beyond blood clotting in these conditions.
Area of Science:
- Neuroscience
- Cardiovascular Biology
- Reproductive Medicine
Background:
- Thrombin, a key coagulation factor, is elevated during pregnancy and preeclampsia (PE).
- Thrombin is also present in the brain, suggesting potential non-hemostatic functions.
- Understanding thrombin's role in the brain during pregnancy and PE is crucial for managing hypertensive disorders.
Purpose of the Study:
- To investigate thrombin expression and its vasoactivity in rat cerebral parenchymal arterioles (PAs) during normal pregnancy and experimental preeclampsia (ePE).
- To assess the impact of thrombin on PA function and its relationship with hemostatic markers in cerebrospinal fluid and plasma.
Main Methods:
- Parenchymal arterioles (PAs) were isolated from nonpregnant (NP), late-pregnant (LP), and ePE rats.
- Vasoactivity of PAs in response to thrombin was measured, with and without inhibition of cyclooxygenase and nitric oxide synthase.
- Plasma and cerebrospinal fluid levels of thrombin-related markers (prothrombin, TAT) and neuronal thrombin expression were quantified using ELISA, Western blot, and immunohistochemistry.
Main Results:
- Prothrombin and thrombin-antithrombin (TAT) levels were higher in ePE plasma compared to NP and LP rats.
- TAT was significantly elevated in cerebrospinal fluid of LP rats compared to NP and ePE rats.
- Thrombin induced moderate vasoconstriction in PAs from all groups, and neuronal thrombin expression decreased in LP and ePE rats.
Conclusions:
- Pregnancy and PE involve altered thrombin levels and expression in the brain.
- Thrombin exhibits vasoactive properties in cerebral arterioles, potentially contributing to hypertensive disorders.
- Findings suggest thrombin has non-coagulant roles in the brain during pregnancy and preeclampsia.
