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

Background The alpha7 nicotinic acetylcholine receptor (α7nAChR) 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-α, IL-1β, IL-2, IL-4, IL-5, IL-7, IL-10, IL-17A, GM-CSF, MCP-1, MIP-1β and IL12(p70)). Conclusions S timulation 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Swedish Research Council, the Swedish Heart-Lung Foundation, Mary von Sydow foundation, Stiftelsen Gamla tjänarinnor, Stiftelsen Tornspiran, Dr. Felix Neuberghs Foundation, Wilhelm and Martina Lundgren foundation and Grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALF GBG-723131). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study protocol was approved by the ethical review board in Gothenburg, Sweden and informed consent was obtained from all participants. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The participant-level datasets used for this report have been deposited with the Swedish National Data Service (, a data repository certified by Core Trust Seal). Due to patient consent and confidentiality agreements, the datasets can be made available for validation purposes by contacting snd{at}snd.gu.se. Data access will be evaluated according to Swedish legislation. Data access for research related questions in the program can be made available by contacting the corresponding author.