Alpha7 nicotinic acetylcholine receptor agonist PHA 568487 dampens inflammation in PBMCs from patients with newly discovered coronary artery disease

Abstract

Background: The alpha7 nicotinic acetylcholine receptor α(7nAChR) controls inflammation in experimental models. The α7nAChR is expressed in human peripheral blood mononuclear cells (PBMCs) as well as in human atherosclerotic plaques, yet, its role in regulating inflammation in patients with cardiovascular disease remains unknown. In this study we aim to investigate whether stimulation of the α7nAChR can dampen the immune response in patients with newly discovered coronary artery disease (CAD). Methods: Human peripheral blood mononuclear cells (PBMCs) extracted from patients with verified CAD (n=38) and control participants with healthy vessels (n=38) were challenged in vitro with lipopolysaccharide (LPS) in combination with α7nAChR agonist PHA 568487. Supernatants were analyzed for cytokines using multiplex immunoassay. The CAD group was re-examined after 6 months. Results: α7nAChR stimulation decreased TNF-α in all groups, in control participants and in CAD patients, both at the first visit as well as the follow-up visit after 6 months. The most pronounced effect of α7nAChR stimulation was seen in CAD patients at their first visit, where 12 of 17 cytokines were decreased (TNF, IL-1β, IL-2, IL-4, IL-5, IL-7, IL-10, IL-17A, GM-CSF, MCP-1, MIP-1β and IL12(p70)). Conclusions: Stimulation of α7nAChR dampens the inflammatory response in human PBMCs. This suggests that the anti-inflammatory properties of the α7nAChR may have a role in treating CAD.