Angiotensin (1-7) ameliorates angiotensin II-induced inflammation by inhibiting LOX-1 expression.

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).

• Authors: Lijun Wang, Xuesong Hu, Wenwu Zhang, Fang Tian
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 62 Issue 2 Pg. 219-28 (Feb 2013) ISSN: 1420-908X [Electronic] Switzerland
• PMID: 23233095 (Publication Type: Journal Article)

Chemical References

• Chemokine CCL2
• NF-kappa B
• Peptide Fragments
• Scavenger Receptors, Class E
• Vascular Cell Adhesion Molecule-1
• Angiotensin II
• DNA
• Angiotensin I
• angiotensin I (1-7)

Topics

• Angiotensin I (metabolism)
• Angiotensin II (metabolism)
• Animals
• Cell Adhesion
• Chemokine CCL2 (metabolism)
• DNA (metabolism)
• Endothelial Cells (drug effects, metabolism)
• Female
• Humans
• Inflammation (metabolism)
• Male
• NF-kappa B (metabolism)
• Peptide Fragments (metabolism)
• Rabbits
• Scavenger Receptors, Class E (antagonists & inhibitors, genetics, metabolism)
• Vascular Cell Adhesion Molecule-1 (metabolism)