Cholinergic signaling through the alpha 7 nicotinic receptor inhibits atherosclerosis in hypercholesterolemic mice (671.7)

Abstract

Objective: The aim was to examine the expression of the alpha 7 nicotinic acetylcholine receptor (α7R) in human atherosclerotic plaques and to investigate α7R effects on progression of atherosclerosis in hypercholesterolemic Ldlr‐/‐ mice.Methods: Human carotid plaques and aortic lesions of hypercholesterolemic mice were stained for α7R, using immunohistochemistry. To study the role of cholinergic signaling in atherosclerosis, male Ldlr‐/‐ mice were lethally irradiated and reconstituted with bone marrow from wildtype (WT) or α7R deficient animals.Results: α7R was detected on T cells and macrophages in human carotid plaques. Ablation of hematopoietic cell α7R in Ldlr‐/‐ mice increased aortic atherosclerosis by 38%. This was accompanied by increased aortic interferon‐γ mRNA, implying increased Th1 activity in the absence of α7R signaling.Conclusion: α7R is expressed by T cells and macrophages in human plaques. Lack of α7R in bone marrow dramatically accelerates atherosclerosis in LDLr‐/‐ mice. The present study suggests that cholinergic signaling through hematopoietic α7R inhibits atherosclerosis by modulating immune inflammation.