Differential regulation of endothelium behavior by progesterone and medroxyprogesterone acetate
| Autor: | P. Cutini, Virginia Massheimer, Adrián Esteban Campelo |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
CIENCIAS MÉDICAS Y DE LA SALUD Endothelium medicine.drug_class Endocrinology Diabetes and Metabolism Medroxyprogesterone Acetate Medicina Clínica Nitric Oxide Nitric oxide chemistry.chemical_compound Endocrinology Cell Movement Internal medicine Vascular Endocrinología y Metabolismo purl.org/becyt/ford/3.2 [https] medicine Medroxyprogesterone acetate Animals LY294002 Rats Wistar Protein kinase C Progesterone Medroxiprogesterone biology Chemistry Endothelial Cells Rats Chelerythrine medicine.anatomical_structure biology.protein Female purl.org/becyt/ford/3 [https] Cyclooxygenase Endothelium Vascular Progestin medicine.drug |
| Zdroj: | CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET |
| Popis: | Medroxyprogesterone acetate (MPA) is a synthetic progestin commonly used in hormone replacement therapy (HRT). The aim of this work was to study and compare the effect of progesterone (Pg) and MPA, on the regulation of cellular events associated with vascular homeostasis and disease. Platelet adhesion to endothelial cells (ECs), nitric oxide (NO) production, and cell migration were studied using murine endothelial cells in vitro exposed to the progestins. After seven minutes treatment, MPA significantly inhibited NO synthesis with respect to control value; meanwhile Pg markedly increased vasoactive production. In senile ECs, the stimulatory action of Pg decreases; meanwhile MPA maintained its ability to inhibit NO synthesis.The presence of RU486 antagonized each steroid action. When ECs were preincubated with PD98059 (MAPK inhibitor) or chelerythrine (PKC inhibitor) before Pg or MPA treatment, the former totally suppressed the steroid action, but the PKC antagonist did not affect NO production. In the presence of a PI3K inhibitor (LY294002) a partial reduction in Pg effect, and a reversal of MPA action was detected. Using indomethacin the contribution of cyclooxygenase (COX) pathway was also detected. On platelet adhesion assays, Pg inhibited and MPA stimulated platelet adhesion to ECs. Under inflammatory conditions, Pg prevented platelet adhesion induced by lipopolysaccharide (LPS); meanwhile MPA potentiated the stimulatory action of LPS. Finally, although both steroids enhanced ECs migration, MPA exhibited a greater effect. In conclusion the data presented in this research provide evidence of a differential regulation of vascular function by Pg and MPA Fil: Cutini, Pablo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina Fil: Campelo, Adrián Esteban. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahia Blanca; Argentina Fil: Massheimer, Virginia Laura. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahia Blanca; Argentina |
| Databáze: | OpenAIRE |
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