Journal
ATHEROSCLEROSIS
Volume 242, Issue 2, Pages 506-514Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2015.08.006
Keywords
Interleukin-22; Smooth muscle cells; Atherosclerosis; Vascular repair
Funding
- Swedish Research Council [K2011-65X-08311-24-6]
- Swedish Heart and Lung Foundation [20140078]
- Swedish Medical Society
- Royal Physiographic Society in Lund
- Swedish Foundation for Strategic Research [SSF-RBa08-0075]
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Objective: IL-22 is a recently discovered cytokine that belongs to the family of IL-10 related cytokines. It is produced by activated T-cells and innate lymphoid cells and has been suggested to be involved in tissue repair. As both inflammation and repair play important roles in atherosclerosis we investigated if IL-22 deficiency influences the disease process in Apoe(-/-) mice. Methods: We generated IL-22(-/-)Apoe(-/-) mice and fed them high-fat-diet for 14 weeks to characterize atherosclerosis development. Results: IL-22(-/-)Apoe(-/-) mice exhibited reduced plaque size both in the aorta (p = 0.0036) and the aortic root compared (p = 0.0012) with Apoe(-/-) controls. Moreover, plaque collagen was reduced in IL-22(-/-)Apoe(-/-) mice (p = 0.02) and this was associated with an increased expression of smooth muscle cell (SMC)-alpha-actin (p = 0.04) and caldesmon (p = 0.016) in the underlying media. Carotid arteries from IL-22(-/-)Apoe(-/-) mice displayed increased expression of genes associated with a contractile SMC phenotype e.g. alpha-actin (p = 0.004) and caldesmon (p = 0.03). Arterial SMCs were shown to express the IL-22 receptor and in vitro exposure to IL-22 resulted in a down-regulation of alpha actin and caldesmon gene expression in these cells. Conclusion: Our observations demonstrate that IL-22 is involved in plaque formation and suggest that IL-22 released by immune cells is involved in activation of vascular repair by stimulating medial SMC dedifferentiation into a synthetic phenotype. This response contributes to plaque growth by enabling SMC migration into the intima but may also help to stabilize the plaque. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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