284 nm UVB Phototherapy Regulates Immunoinflammatory Responses and Improves Atherosclerotic Plaque Stability in Mice.

AIM: We previously reported that broad-band and specific wavelengths of ultraviolet B (UVB) limit the development of atherosclerosis by augmenting anti-inflammatory immune responses in hypercholesterolemic mice. This study aimed to elucidate the effect of 284 nm UVB on the stabilization of atherosclerotic plaques and the underlying mechanisms. METHODS AND RESULTS: Six- to eight-week-old male LDL receptor-deficient (Ldlr (-/-)) mice were fed a high-fat and high-cholesterol diet for 8 weeks to form atherosclerotic lesions, and the diet was changed to a standard diet. The mice were subsequently irradiated with 284 nm UVB at 5 kJ/m(2) twice weekly for 2 or 4 weeks. The effects of 284 nm UVB irradiation on atherosclerotic plaque size and components and immunoinflammatory responses were evaluated by histological analysis and flow cytometry. Normalization of plasma cholesterol levels did not prevent the development of atherosclerotic lesions in the aortic sinus of UVB-irradiated or nonirradiated mice, whereas it markedly reduced the lipid content in the aortic sinus lesions of these mice, which was more prominent in UVB-irradiated mice. The accumulation of CD4(+) T cells in atherosclerotic lesions and aortic immunoinflammatory responses were reduced in UVB-irradiated mice, although no beneficial effects of UVB treatment on macrophage accumulation or collagen content were observed. The plaque-stabilizing effect of UVB treatment was associated with augmented regulatory T cell immune responses in lymphoid tissues. CONCLUSIONS: 284 nm UVB irradiation in combination with lipid-lowering therapy improves the stability of atherosclerotic plaques by augmenting anti-inflammatory Treg immune responses. The combination of aggressive lipid-lowering therapies and 284 nm UVB phototherapy may serve as an attractive therapeutic approach for high-risk patients with vulnerable atherosclerotic plaques.