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.

Puerarin protects endothelial progenitor cells from damage of angiotensin II via activation of ERK1/2‑Nrf2 signaling pathway

“…EPCs may be a potential therapeutic target for vascular repair and regeneration, due to their strong capacity for proliferation and differentiation (20). However, studies have reported that EPCs may be damaged by Ang II and there is evidence that Ang II upregulates the levels of pro-inflammatory cytokines (including IL-6, monocyte chemoattractant protein-1 and VCAM-1) via the type 1 Ang II receptor, which may deteriorate the atherosclerotic inflammatory response (21,22). Consistent with previous studies, the results of the present study suggested that cell proliferation and migration were decreased by Ang II, and it was demonstrated that 1.0 µM Ang II stimulated ROS production to increase EPC senescence, and increased the expression of ICAM-1 and VCAM-1, two adhesion molecules of EPCs.…”

MicroRNA-145 is involved in endothelial cell dysfunction and acts as a promising biomarker of acute coronary syndrome

“…miR-145 has been investigated in some other human diseases, such as malignancy [28], diabetes [29] and also other cardiovascular disease [30]. The functional role of miR-145 in the diseases above has been uncovered.…”

Cucumis sativus Aqueous Fraction Inhibits Angiotensin II-Induced Inflammation and Oxidative Stress In Vitro

“…Ang II also has prooxidant effects and induces a decrease in NO bioavailability [ 5 , 13 ]. Upon binding AT1R, it triggers the signaling pathway that activates NADH oxidase to produce O 2 ∙− [ 4 ], increasing the intracellular concentration of this radical ion, and overcoming cellular antioxidant mechanisms (superoxide dismutase, catalase, and glutathione peroxidase).…”

“…The presence of ROS is detected by proteins sensitive to the redox status of the cell; in turn, these proteins activate AKT (Protein kinase B), MAPKs (mitogen-activated protein kinases), and NF-κB (Nuclear factor kappa B) [ 7 , 8 , 9 , 10 ], triggering inflammation and promoting the synthesis of IL-1β, IL-6, TNF-α, C reactive protein, E-selectin, ICAM-1 (Intercellular Adhesion Molecule 1), VCAM-1 (Vascular cell adhesion protein 1), and MCP-1 (Monocyte chemoattractant protein-1), among other molecules [ 11 , 12 , 13 , 14 ].…”