Open Access Commentary

Is atherosclerosis an autoimmune disease?

Eiji Matsuura12*, Fabiola Atzeni3, Piercarlo Sarzi-Puttini3, Maurizio Turiel4, Luis R Lopez5 and Michael T Nurmohamed6

Author Affiliations

1 Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan

2 Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan

3 Rheumatology Unit, L. Sacco University Hospital of Milan, Milan, Italy

4 Cardiology Unit, Department of Biomedical Sciences for Health, Galeazzi Orthopedic Institute IRCCS, University of Milan, Milan, Italy

5 Medical Department, Corgenix Inc, Broomfield, CO, USA

6 VU University Medical Center and Jan van Breemen Research Institute, Amsterdam, Netherlands

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BMC Medicine 2014, 12:47  doi:10.1186/1741-7015-12-47

Published: 18 March 2014


Immunologic research into pathogenic mechanisms operating in autoimmune-mediated atherosclerosis initially focused on adaptive immunity. Current interest is directed to more basic inflammatory mechanisms. Chronic inflammation (innate immunity-associated) may trigger initial events that can lead to atherosclerotic cardiovascular disease. This chronic inflammation may start early in life and be perpetuated by classic atherosclerosis risk factors. Lipid peroxidation of low-density lipoprotein seems to be a key event in the initiation and progression of atherosclerosis. Oxidized low-density lipoprotein triggers inflammatory and immunogenic events that promote endothelial dysfunction and the synthesis and secretion of pro-inflammatory cytokines, leading to an autoimmune response capable of accelerating the intracellular accumulation of lipids within atherosclerotic plaques. Oxidized low-density lipoprotein binds β2-glycoprotein I to form circulating complexes found in both autoimmune and non-autoimmune atherosclerosis. It is likely that β2-glycoprotein I and/or these complexes contribute to early atherogenesis by stimulating pro-inflammatory innate immunity through endogenous sensors and inflammasome/interleukin-1 pathways. We discuss the chronic inflammatory (innate) and autoimmune (adaptive) responses operating in atherosclerosis to discern the role of autoimmunity in atherosclerotic cardiovascular disease.

Atherosclerosis; Auto-inflammatory disease; Autoimmunity; β2-glycoprotein I; Innate immunity; Inflammasome; Oxidized LDL