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Statins Prevent the Deleterious Consequences of Placental Chemerin Upregulation in Preeclampsia.
Tan, Lunbo; Kluivers, Ans C M; Cruz-López, Edwyn O; Broekhuizen, Michelle; Chen, Zhongli; Neuman, Rugina I; Schoenmakers, Sam; Ruijgrok, Liesbeth; van de Velde, Daan; de Winter, Brenda C M; van den Bogaerdt, Antoon J; Lu, Xifeng; Danser, A H Jan; Verdonk, Koen.
Afiliación
  • 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.
  • Kluivers ACM; Clinical Research Center, The First Affiliated Hospital of Shantou University Medical College, China (L.T., X.L.).
  • 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; Department of Obstetrics and Gynecology (A.C.M.K., R.I.N., S.S.), Erasmus MC, Rotterdam, the Netherlands.
  • Chen Z; 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.
  • 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.
  • Schoenmakers S; Division of Neonatology, Department of Neonatal and Pediatric Intensive Care (M.B.), Erasmus MC, Rotterdam, the Netherlands.
  • Ruijgrok L; Department of Internal Medicine, Academic Center for Thyroid Diseases (Z.C.), Erasmus MC, Rotterdam, the Netherlands.
  • van de Velde D; 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.
  • de Winter BCM; Department of Obstetrics and Gynecology (A.C.M.K., R.I.N., S.S.), Erasmus MC, Rotterdam, the Netherlands.
  • van den Bogaerdt AJ; Department of Obstetrics and Gynecology (A.C.M.K., R.I.N., S.S.), Erasmus MC, Rotterdam, the Netherlands.
  • Lu X; Department of Hospital Pharmacy (L.R., D.v.d.V., B.C.M.d.W.), Erasmus MC, Rotterdam, the Netherlands.
  • Danser AHJ; Department of Hospital Pharmacy (L.R., D.v.d.V., B.C.M.d.W.), Erasmus MC, Rotterdam, the Netherlands.
  • Verdonk K; Department of Hospital Pharmacy (L.R., D.v.d.V., B.C.M.d.W.), Erasmus MC, Rotterdam, the Netherlands.
Hypertension ; 81(4): 861-875, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38361240
ABSTRACT

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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Preeclampsia / Inhibidores de Hidroximetilglutaril-CoA Reductasas Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Female / Humans / Pregnancy Idioma: En Revista: Hypertension Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Preeclampsia / Inhibidores de Hidroximetilglutaril-CoA Reductasas Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Female / Humans / Pregnancy Idioma: En Revista: Hypertension Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos