Abstract
BackgroundRisk 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.MethodsTopical 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.ResultsTPA 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.ConclusionsTPA-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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12895-016-0046-1) contains supplementary material, which is available to authorized users.
Highlights
Risk of cardiovascular disease is increased in patients with psoriasis, but molecular mechanisms linking the two conditions have not been clearly established
Long-term application of TPA induces ear swelling and local inflammation in ApoE−/− mice To induce psoriasis-like skin inflammation, hypercholesterolaemic ApoE−/− mice received twice weekly topical applications on both ears of either TPA or vehicle, for 8 weeks
A maximum severity psoriasis lesion with 6 % of total body area involvement corresponds to a Psoriasis Area Severity Index (PASI, the most widely used tool to clinically assess psoriasis severity) of 5, compatible with mild-to-moderate disease [35]. We found that these skin lesions elicited unequivocal signs of increased systemic inflammation and it is notable that even mild psoriasis has been associated with increased risk of myocardial infarction and stroke [2, 3]
Summary
Risk of cardiovascular disease is increased in patients with psoriasis, but molecular mechanisms linking the two conditions have not been clearly established. Epidemiological studies have demonstrated that psoriasis is associated with increased risk of cardiovascular disease, e.g., myocardial infarction, stroke, and cardiovascular death [2,3,4,5,6]. This association has led to recommendations for screening. The lack of appropriate models to study potential causal links between psoriasis and cardiovascular disease has hampered such investigations. Development of an animal model with psoriasis-like skin lesions and atherosclerosis would provide a valuable tool for investigations of putative shared disease mechanisms and potential new therapeutic targets aimed at both diseases. Interleukin (IL)-17producing cells have been found to have a key role in the pathogenesis of both psoriasis and atherosclerosis, even though the exact role of Th17 cells in atherogenesis remains debated [14]
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