A novel mouse model for psoriasis-atherosclerosis (PSO-AS) comorbidity

This study aims to establish and validate a novel psoriasis-atherosclerosis comorbidity (PSO-AS) animal model to explore the pathogenesis and therapeutic strategies for these conditions. Psoriasis (PSO) is a chronic, inflammatory skin disorder, and atherosclerosis (AS) is a cardiovascular disease characterized by plaque buildup in arteries. Both conditions share common inflammatory pathways, such as the IL-23/IL-17 axis and platelet involvement. Numerous studies demonstrated that patients with psoriasis are at an extremely elevated risk for atherosclerotic cardiovascular disease (ASCVD) events, particularly atherosclerosis. We aimed to establish and validate a novel psoriasis-atherosclerosis comorbidity (PSO-AS) animal model using apolipoprotein E-deficient (ApoE−/− ) mice. The model was constructed by combining high-fat diet-induced atherosclerosis with imiquimod (IMQ)-triggered psoriatic inflammation. Starting at 8 weeks of age, ApoE−/− mice were fed a high-fat diet until 20 weeks. At 16 weeks, the dorsal hair was partially removed, and 5% IMQ cream (50 mg) was topically applied to the denuded skin for five consecutive days followed by a two-day rest, cyclically until termination. Histopathological analysis of psoriatic lesions revealed epidermal hyperplasia, hyperkeratosis, parakeratosis, and dermal inflammatory infiltration via hematoxylin-eosin (HE) staining. Quantitative PCR (qPCR) demonstrated significantly elevated expression of psoriatic cytokines (IL-17A, IL-17F, IL-22, IL-1β), antimicrobial peptides (S100a8, S100a9) and chemokines (CXCL1, CXCL2, CXCL5, CCL20) in psoriatic lesions compared to atherosclerosis-only controls. Serum ELISA confirmed increased levels of systemic inflammatory and psoriatic markers, including TNF-α, IL-6, IL-23, and IL-17A. Atherosclerotic plaque progression was assessed by en face Oil Red O staining, showing significantly larger plaque areas in the PSO-AS group. Aortic root sections further revealed thinner fibrous caps, larger necrotic cores, and advanced pathological remodeling in the PSO-AS cohort. This dual-disease model successfully recapitulates the synergistic exacerbation of psoriasis and atherosclerosis, complying with the clinical phenomena that PSO could exacerbate the progression of AS, providing a robust platform for mechanistic exploration and therapeutic evaluation of this significant comorbidity.