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

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. copyright © 2014 weijuan li et al.