Abstract
Objective and design
Endothelial dysfunction plays an important role in all stages of atherosclerosis and is characterized by an increased proinflammatory response. This study investigated the effect of angiotensin (1–7) on angiotensin II (Ang II)-mediated inflammation in endothelial cells (ECs) and uncovered its molecular mechanism.
Methods and results
Real-time PCR and western blot analysis were used to determine lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression. Ang II treatment induced inflammation, as measured by the production of vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1, by activating nuclear factor-κB (NF-κB) in ECs. Ang II also induced LOX-1 expression in human ECs and rabbit aortic ECs. LOX-1 played an essential role in Ang II-mediated inflammation because Ang II antagonists or small interference RNA significantly decreased Ang II-induced VCAM-1 production. LOX-1 overexpression enhanced Ang II-mediated inflammation. LOX-1 mediated Ang II-induced inflammation by inducing NF-κB DNA-binding activity. Angiotensin (1–7) inhibited LOX-1 expression and diminished Ang II-mediated inflammation in ECs.
Conclusions
Our findings suggest that angiotensin (1–7) prevents Ang II-induced inflammation by inhibiting LOX-1 mRNA and protein expression in ECs and may represent a novel pleiotropic effect of angiotensin (1–7).
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Wang, L., Hu, X., Zhang, W. et al. Angiotensin (1–7) ameliorates angiotensin II-induced inflammation by inhibiting LOX-1 expression. Inflamm. Res. 62, 219–228 (2013). https://doi.org/10.1007/s00011-012-0571-2
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DOI: https://doi.org/10.1007/s00011-012-0571-2