Aldosterone modulates endothelial permeability and endothelial nitric oxide synthase activity by rearrangement of the actin cytoskeleton
Autor: | Marion Haubitz, Michaela Beese, Hermann Haller, Uwe Klinge, Kristin Wyss, Anette Fiebeler, Torsten Kirsch |
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Rok vydání: | 2012 |
Předmět: |
endocrine system
medicine.medical_specialty RHOA Endothelium Hydrocortisone Nitric Oxide Synthase Type III Vascular permeability Cell junction Permeability Adherens junction Mineralocorticoid receptor Internal medicine Internal Medicine medicine Human Umbilical Vein Endothelial Cells Humans Phosphorylation Aldosterone Cytoskeleton biology Tight junction Endothelial Cells Actin cytoskeleton Actins Cell biology Endocrinology medicine.anatomical_structure Receptors Mineralocorticoid biology.protein Endothelium Vascular rhoA GTP-Binding Protein Proto-Oncogene Proteins c-akt Signal Transduction |
Zdroj: | Hypertension (Dallas, Tex. : 1979). 61(2) |
ISSN: | 1524-4563 |
Popis: | Aldosterone (Aldo) is involved in vascular remodeling and inflammation; however, the mechanisms are imperfectly defined. We hypothesized that Aldo alters endothelial integrity and modifies paracellular permeability. Human umbilical vein endothelial cells were exposed to Aldo (10 –9 mol/L) and alterations in paracellular permeability, assembly of tight and adherens junctions and activation of intracellular signaling pathways were determined. Aldo increased endothelial permeability for molecules ≤70 kDa within 60 minutes. A transient loss of cortical actin with formation of actin stress fibers and disruption of continuous adherens and tight junction strands accompanied these changes. Mineralocorticoid receptor blockade, inhibition of RhoA, or disruption of extracellular-regulated protein kinase1/2 signaling pathways attenuated the Aldo-related effects. Moreover, Aldo-induced cytoskeletal rearrangement led to rapid dephosphorylation of protein kinase B and subsequent deactivation of endothelial nitric oxide synthase. Ex vivo tracer flux experiments with Evans blue–conjugated albumin demonstrated a concordant response to Aldo in freshly isolated umbilical arteries. Furthermore, low-dose cortisol (3×10 –10 to 3×10 –9 mol/L) mimics the effect of Aldo on endothelial integrity, and Aldo, by upregulating11β-hydroxysteroid dehydrogenase type 2, might even aggravate this deleterious effect of low-dose cortisol. We suggest that these mechanisms may contribute to the vasculopathy induced by inappropriate mineralocorticoid receptor activation. |
Databáze: | OpenAIRE |
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