Change of concept about the regulation of angiotensin II-induced monocyte chemoattractant protein-1 production in human endothelial cells
Autor: | Mercedes González-Peteiro, Beatriz Paradela-Dobarro, A.L. Batista-Oliveira, Ezequiel Álvarez, José Ramón González-Juanatey, Bruno K. Rodiño-Janeiro, S Raposeiras-Roubin, María Isabel Castiñeiras-Landeira |
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Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Angiotensin receptor medicine.medical_specialty Physiology Cell Survival Cell Culture Techniques Angiotensin II Type 2 Receptor Blockers 030204 cardiovascular system & hematology Receptor Angiotensin Type 2 Receptor Angiotensin Type 1 03 medical and health sciences 0302 clinical medicine NADPH oxidase complex Superoxides Internal medicine medicine Human Umbilical Vein Endothelial Cells Humans Receptor Chemokine CCL2 Pharmacology NADPH oxidase Angiotensin II receptor type 1 biology Chemistry Reverse Transcriptase Polymerase Chain Reaction Angiotensin II Transcription Factor RelA NOX4 Endothelial Cells Angiotensin-converting enzyme Immunohistochemistry Cell biology Protein Subunits 030104 developmental biology Endocrinology Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization cardiovascular system biology.protein Molecular Medicine Angiotensin II Type 1 Receptor Blockers hormones hormone substitutes and hormone antagonists NADP |
Zdroj: | Vascular pharmacology. 80 |
ISSN: | 1879-3649 |
Popis: | Aims: Some intriguing clinical observations about the anti-inflammatory effects of angiotensin type 1 (AT1) receptor blockers and angiotensin converting enzyme inhibitors in cardiovascular patients brought us to study the signalling pathways which lead to angiotensin II (ANG)-induced monocyte chemoattractant protein-1 (MCP-1) production in human endothelial cells. Methods: MCP-1 production in human umbilical vein endothelial cells (HUVECs) under treatments with ANG, AT1 and angiotensin type 2 (AT2) receptor blockers and pravastatin was measured by ELISA. The expression of AT1 and AT2 receptors and NADPH oxidase catalytic subunits (NOX 1-5) was analysed at mRNA and protein levels. Nuclear factor-kappa B (NF-κB) activation was studied by p65 subunit translocation to the cellular nucleus. Cell viability was tested by the MTT method. Nox4 subcellular distribution was analysed by subcellular protein fractionation and by immunoprecipitation followed by matrix-assisted laser desorption/ionization mass spectrometry analysis. Results: ANG-induced MCP-1 production was mediated by AT2 receptor, but not AT1 receptor in HUVECs in culture, which in turn activated NF-κB, promoting p65 subunit translocation to the nucleus. Reactive oxygen species produced by NADPH oxidase participated in this activation, mainly by the Nox4 subunit, ubiquitously expressed in all the compartments of HUVECs. Pravastatin inhibited ANG-induced MCP-1 production. Conclusions: Our results support that ANG-induced MCP-1 production in HUVECs is mediated by AT2 instead AT1 receptor activation, which in turn activates NF-κB involving reactive oxygen species produced by the NADPH oxidase complex. Statins can also block ANG-induced MCP-1 production, probably by their inhibitory effects on NADPH oxidase activity. |
Databáze: | OpenAIRE |
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