Statins Prevent the Deleterious Consequences of Placental Chemerin Upregulation in Preeclampsia.

Autor:	Tan L; Division of Vascular Medicine and Pharmacology, Department of Internal Medicine (L.T., A.C.M.K., E.O.C.-L., M.B., R.I.N., A.H.J.D., K.V.), Erasmus MC, Rotterdam, the Netherlands.; Clinical Research Center, The First Affiliated Hospital of Shantou University Medical College, China (L.T., X.L.)., Kluivers ACM; Division of Vascular Medicine and Pharmacology, Department of Internal Medicine (L.T., A.C.M.K., E.O.C.-L., M.B., R.I.N., A.H.J.D., K.V.), Erasmus MC, Rotterdam, the Netherlands.; Department of Obstetrics and Gynecology (A.C.M.K., R.I.N., S.S.), Erasmus MC, Rotterdam, the Netherlands., Cruz-López EO; Division of Vascular Medicine and Pharmacology, Department of Internal Medicine (L.T., A.C.M.K., E.O.C.-L., M.B., R.I.N., A.H.J.D., K.V.), Erasmus MC, Rotterdam, the Netherlands., Broekhuizen M; Division of Vascular Medicine and Pharmacology, Department of Internal Medicine (L.T., A.C.M.K., E.O.C.-L., M.B., R.I.N., A.H.J.D., K.V.), Erasmus MC, Rotterdam, the Netherlands.; Division of Neonatology, Department of Neonatal and Pediatric Intensive Care (M.B.), Erasmus MC, Rotterdam, the Netherlands., Chen Z; Department of Internal Medicine, Academic Center for Thyroid Diseases (Z.C.), Erasmus MC, Rotterdam, the Netherlands., Neuman RI; Division of Vascular Medicine and Pharmacology, Department of Internal Medicine (L.T., A.C.M.K., E.O.C.-L., M.B., R.I.N., A.H.J.D., K.V.), Erasmus MC, Rotterdam, the Netherlands.; Department of Obstetrics and Gynecology (A.C.M.K., R.I.N., S.S.), Erasmus MC, Rotterdam, the Netherlands., Schoenmakers S; Department of Obstetrics and Gynecology (A.C.M.K., R.I.N., S.S.), Erasmus MC, Rotterdam, the Netherlands., Ruijgrok L; Department of Hospital Pharmacy (L.R., D.v.d.V., B.C.M.d.W.), Erasmus MC, Rotterdam, the Netherlands., van de Velde D; Department of Hospital Pharmacy (L.R., D.v.d.V., B.C.M.d.W.), Erasmus MC, Rotterdam, the Netherlands., de Winter BCM; Department of Hospital Pharmacy (L.R., D.v.d.V., B.C.M.d.W.), Erasmus MC, Rotterdam, the Netherlands., van den Bogaerdt AJ; Heart Valve Department, Euro Tissue Bank-Bio Implant Services LIFE (ETB-BISLIFE), Beverwijk, the Netherlands (A.J.v.d.B.)., Lu X; Clinical Research Center, The First Affiliated Hospital of Shantou University Medical College, China (L.T., X.L.)., Danser AHJ; Division of Vascular Medicine and Pharmacology, Department of Internal Medicine (L.T., A.C.M.K., E.O.C.-L., M.B., R.I.N., A.H.J.D., K.V.), Erasmus MC, Rotterdam, the Netherlands., Verdonk K; Division of Vascular Medicine and Pharmacology, Department of Internal Medicine (L.T., A.C.M.K., E.O.C.-L., M.B., R.I.N., A.H.J.D., K.V.), Erasmus MC, Rotterdam, the Netherlands.
Jazyk:	angličtina
Zdroj:	Hypertension (Dallas, Tex. : 1979) [Hypertension] 2024 Apr; Vol. 81 (4), pp. 861-875. Date of Electronic Publication: 2024 Feb 15.
DOI:	10.1161/HYPERTENSIONAHA.123.22457
Abstrakt:	Background: Chemerin, an inflammatory adipokine, is upregulated in preeclampsia, and its placental overexpression results in preeclampsia-like symptoms in mice. Statins may lower chemerin. Methods: Chemerin was determined in a prospective cohort study in women suspected of preeclampsia and evaluated as a predictor versus the sFlt-1 (soluble fms-like tyrosine kinase-1)/PlGF (placental growth factor) ratio. Chemerin release was studied in perfused placentas and placental explants with or without the statins pravastatin and fluvastatin. We also addressed statin placental passage and the effects of chemerin in chorionic plate arteries. Results: Serum chemerin was elevated in women with preeclampsia, and its addition to a predictive model yielded significant effects on top of the sFlt-1/PlGF ratio to predict preeclampsia and its fetal complications. Perfused placentas and explants of preeclamptic women released more chemerin and sFlt-1 and less PlGF than those of healthy pregnant women. Statins reversed this. Both statins entered the fetal compartment, and the fetal/maternal concentration ratio of pravastatin was twice that of fluvastatin. Chemerin constricted plate arteries, and this was blocked by a chemerin receptor antagonist and pravastatin. Chemerin did not potentiate endothelin-1 in chorionic plate arteries. In explants, statins upregulated low-density lipoprotein receptor expression, which relies on the same transcription factor as chemerin, and NO release. Conclusions: Chemerin is a biomarker for preeclampsia, and statins both prevent its placental upregulation and effects, in an NO and low-density lipoprotein receptor-dependent manner. Combined with their capacity to improve the sFlt-1/PlGF ratio, this offers an attractive mechanism by which statins may prevent or treat preeclampsia. Competing Interests: None.
Databáze:	MEDLINE
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