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
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
Externí odkaz: