Arterial and Venous Endothelia Display Differential Functional Fractalkine (CX 3 CL1) Expression by Angiotensin-II
| Autor: | Cristina Rius, Laura Piqueras, Herminia González-Navarro, Fernando Albertos, Chantal Company, Concha López-Ginés, Andreas Ludwig, Jose-Ignacio Blanes, Esteban J. Morcillo, Maria-Jesus Sanz |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Pathology Time Factors p38 Mitogen-Activated Protein Kinases Mice Venules Leukocytes Endothelial dysfunction Extracellular Signal-Regulated MAP Kinases Receptor Cells Cultured Mice Knockout Membrane Glycoproteins Angiotensin II NF-kappa B Arteries Endothelial stem cell Arterioles NADPH Oxidase 5 NADPH Oxidase 4 NADPH Oxidase 2 Female RNA Interference Receptors Chemokine Tumor necrosis factor alpha Cardiology and Cardiovascular Medicine Signal Transduction medicine.medical_specialty CX3C Chemokine Receptor 1 Biology Transfection Peripheral blood mononuclear cell Losartan Veins Interferon-gamma Apolipoproteins E Downregulation and upregulation Internal medicine Cell Adhesion Human Umbilical Vein Endothelial Cells medicine Animals Humans Leukocyte Rolling CX3CL1 Chemokine CX3CL1 Tumor Necrosis Factor-alpha Endothelial Cells Membrane Proteins NADPH Oxidases Atherosclerosis medicine.disease Mice Inbred C57BL Disease Models Animal Endocrinology Angiotensin II Type 1 Receptor Blockers |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 33:96-104 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/atvbaha.112.254870 |
| Popis: | Objective— Angiotensin-II (Ang-II) promotes the interaction of mononuclear cells with arterioles and neutrophils with postcapillary venules. To investigate the mechanisms underlying this dissimilar response, the involvement of fractalkine (CX 3 CL1) was explored. Methods and Results— Enhanced CX 3 CL1 expression was detected in both cremasteric arterioles and postcapillary venules 24 hours after Ang-II intrascrotal injection. Arteriolar leukocyte adhesion was the unique parameter significantly reduced (83%) in animals lacking CX 3 CL1 receptor (CX 3 CR1). Human umbilical arterial and venous endothelial cell stimulation with 1 μmol/L Ang-II increased CX 3 CL1 expression, yet neutralization of CX 3 CL1 activity only significantly inhibited Ang-II–induced mononuclear cell–human umbilical arterial endothelial cell interactions (73%) but not with human umbilical venous endothelial cells. The use of small interfering RNA revealed the involvement of tumor necrosis factor-α in Ang-II–induced CX 3 CL1 upregulation and mononuclear cell arrest. Nox5 knockdown with small interfering RNA or pharmacological inhibition of extracellular signal-regulated kinases1/2, p38 mitogen-activated protein kinase, and nuclear factor-κB also abolished these responses. Finally, when human umbilical arterial endothelial cells were costimulated with Ang-II, tumor necrosis factor-α, and interferon-γ, CX 3 CL1 expression and mononuclear cell adhesiveness were more pronounced than when each stimulus was provided alone. Conclusion— These results suggest that Ang-II induces functional CX 3 CL1 expression in arterial but not in venous endothelia. Thus, targeting endothelial CX 3 CL1–mononuclear leukocyte CX 3 CR1 interactions may constitute a new therapeutic strategy in the treatment of Ang-II–associated cardiovascular diseases. |
| Databáze: | OpenAIRE |
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