Autoantibodies targeting AT1 receptor from patients with acute coronary syndrome upregulate proinflammatory cytokines expression in endothelial cells involving NF-κB pathway.

Abstract

Our study intended to prove whether agonistic autoantibodies to angiotensin II type 1 receptor (AT1-AAs) exist in patients with coronary heart disease (CHD) and affect the human endothelial cell (HEC) by upregulating proinflammatory cytokines expression involved in NF-κB pathway. Antibodies were determined by chronotropic responses of cultured neonatal rat cardiomyocytes coupled with receptor-specific antagonists (valsartan and AT1-EC2) as described previously. Interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), and monocyte chemotactic protein-1 (MCP-1) expression were improved at both mRNA and protein levels in HEC, while NF-κB in the DNA level was improved detected by electrophoretic mobility shift assays (EMSA). These improvements could be inhibited by specific AT1 receptor blocker valsartan, NF-κB blocker pyrrolidine dithiocarbamate (PDTC), and specific short peptides from the second extracellular loop of AT1 receptor. These results suggested that AT1-AAs, via the AT1 receptor, induce expression of proinflammatory cytokines involved in the activation of NF-κB. AT1-AAs may play a great role in the pathogenesis of the acute coronary syndrome by mediating vascular inflammatory effects involved in the NF-κB pathway.

• Authors: Weijuan Li, Zhi Li, Yaoqi Chen, Songhai Li, Yuanyuan Lv, Wenping Zhou, Mengyang Liao, Feng Zhu, Zihua Zhou, Xiang Cheng, Qiutang Zeng, Yuhua Liao, Yumiao Wei
• Journal: Journal of immunology research (J Immunol Res) Vol. 2014 Pg. 342693 ( 2014) ISSN: 2314-7156 [Electronic] Egypt
• PMID: 25762441 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin Receptor Antagonists
• Autoantibodies
• Autoantigens
• Chemokine CCL2
• Inflammation Mediators
• Interleukin-6
• NF-kappa B
• Peptide Fragments
• Receptor, Angiotensin, Type 1
• Thiocarbamates
• Vascular Cell Adhesion Molecule-1
• prolinedithiocarbamate
• Valsartan
• Proline

Topics

• Acute Coronary Syndrome (immunology)
• Angiotensin Receptor Antagonists (pharmacology)
• Animals
• Autoantibodies (metabolism)
• Autoantigens (immunology)
• Cells, Cultured
• Chemokine CCL2 (metabolism)
• Endothelial Cells (immunology)
• Humans
• Inflammation Mediators (metabolism)
• Interleukin-6 (metabolism)
• Myocytes, Cardiac (metabolism)
• NF-kappa B (genetics, metabolism)
• Peptide Fragments (chemical synthesis, immunology)
• Proline (analogs & derivatives, pharmacology)
• Rats
• Receptor, Angiotensin, Type 1 (agonists, chemistry, immunology)
• Thiocarbamates (pharmacology)
• Valsartan (pharmacology)
• Vascular Cell Adhesion Molecule-1 (metabolism)