Effect of 12-O-tetradecanoylphorbol-13-acetate-induced psoriasis-like skin lesions on systemic inflammation and atherosclerosis in hypercholesterolaemic apolipoprotein E deficient mice

TY - JOUR

T1 - Effect of 12-O-tetradecanoylphorbol-13-acetate-induced psoriasis-like skin lesions on systemic inflammation and atherosclerosis in hypercholesterolaemic apolipoprotein E deficient mice

AU - Madsen, Marie

AU - Hansen, Peter Riis

AU - Nielsen, Lars Bo

AU - Hartvigsen, Karsten

AU - Pedersen, Anders Elm

AU - Christensen, Jan Pravsgaard

AU - Pedersen, Annemarie Aarup

AU - Pedersen, Tanja Xenia

PY - 2016/7/11

Y1 - 2016/7/11

N2 - BACKGROUND: Risk of cardiovascular disease is increased in patients with psoriasis, but molecular mechanisms linking the two conditions have not been clearly established. Lack of appropriate animal models has hampered generation of new knowledge in this area of research and we therefore sought to develop an animal model with combined atherosclerosis and psoriasis-like skin inflammation.METHODS: Topical 12-O-tetradecanoylphorbol-13-acetate (TPA) was applied to the ears twice per week for 8 weeks in atherosclerosis-prone apolipoprotein E deficient (ApoE(-/-)) mice.RESULTS: TPA led to localized skin inflammation with increased epidermal thickness, infiltration of inflammatory-like cells and augmented tissue interleukin-17F levels. Systemic effects of the topical application of TPA were demonstrated by increased plasma concentration of serum amyloid A and splenic immune modulation, respectively. However, atherosclerotic plaque area and composition, and mRNA levels of several inflammatory genes in the aortic wall were not significantly affected by TPA-induced skin inflammation.CONCLUSIONS: TPA-induced psoriasis-like skin inflammation in atherosclerosis-prone ApoE(-/-) mice evoked systemic immune-inflammatory effects, but did not affect atherogenesis. The results may question the role of psoriasis-induced inflammation in the pathogenesis of atherosclerosis in psoriasis patients.

AB - BACKGROUND: Risk of cardiovascular disease is increased in patients with psoriasis, but molecular mechanisms linking the two conditions have not been clearly established. Lack of appropriate animal models has hampered generation of new knowledge in this area of research and we therefore sought to develop an animal model with combined atherosclerosis and psoriasis-like skin inflammation.METHODS: Topical 12-O-tetradecanoylphorbol-13-acetate (TPA) was applied to the ears twice per week for 8 weeks in atherosclerosis-prone apolipoprotein E deficient (ApoE(-/-)) mice.RESULTS: TPA led to localized skin inflammation with increased epidermal thickness, infiltration of inflammatory-like cells and augmented tissue interleukin-17F levels. Systemic effects of the topical application of TPA were demonstrated by increased plasma concentration of serum amyloid A and splenic immune modulation, respectively. However, atherosclerotic plaque area and composition, and mRNA levels of several inflammatory genes in the aortic wall were not significantly affected by TPA-induced skin inflammation.CONCLUSIONS: TPA-induced psoriasis-like skin inflammation in atherosclerosis-prone ApoE(-/-) mice evoked systemic immune-inflammatory effects, but did not affect atherogenesis. The results may question the role of psoriasis-induced inflammation in the pathogenesis of atherosclerosis in psoriasis patients.

U2 - 10.1186/s12895-016-0046-1

DO - 10.1186/s12895-016-0046-1

M3 - Journal article

C2 - 27401543

SN - 1471-5945

VL - 16

JO - BMC Dermatology

JF - BMC Dermatology

M1 - 9

ER -