IL-22 affects smooth muscle cell phenotype and plaque formation in apolipoprotein E knockout mice

• Published in: Atherosclerosis Vol. 242; no. 2; pp. 506 - 514
• Main Authors: Rattik, Sara, Hultman, Karin, Rauch, Uwe, Söderberg, Ingrid, Sundius, Lena, Ljungcrantz, Irena, Hultgårdh-Nilsson, Anna, Wigren, Maria, Björkbacka, Harry, Fredrikson, Gunilla Nordin, Nilsson, Jan
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01-10-2015
• Subjects: Animals; Aorta - pathology; Apolipoproteins E - genetics; Atherosclerosis; Atherosclerosis - genetics; Blood Glucose - analysis; Cardiac and Cardiovascular Systems; Cardiovascular; Cholesterol - blood; Clinical Medicine; Enzyme-Linked Immunosorbent Assay; Female; Inflammation; Interleukin-22; Interleukins - genetics; Kardiologi; Klinisk medicin; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocytes, Smooth Muscle - cytology; Phenotype; Plaque, Atherosclerotic - metabolism; Real-Time Polymerase Chain Reaction; Receptors, Interleukin - metabolism; Smooth muscle cells; Triglycerides - blood; Vascular repair; Smooth muscle cells; Vascular repair; Interleukin-22; Atherosclerosis
• ISSN: 0021-9150; 1879-1484; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2015.08.006

Abstract 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)-α-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. α-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.