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

Journal of Immunology Research
Weijuan LiYumiao Wei

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.

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Citations

Aug 29, 2020·European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery·Alessandro GonfiottiLuca Voltolini
May 28, 2020·International Journal of Molecular Sciences·Jaideep ChakladarWeg M Ongkeko
Apr 3, 2021·Frontiers in Endocrinology·Johnny S YounisZaid Abassi
Mar 5, 2021·Journal of Cardiovascular Pharmacology·Juliana Calfa VilhenaCristiane Aguiar da Costa

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Methods Mentioned

BETA
ELISA
Polymerase Chain Reaction
PCR
protein assay
nuclear translocation

Software Mentioned

NIH Image J
Quantity One
SigmaStat

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