Psoriasis-induced acceleration of atherogenesis: a novel murine mouse model

Authors

• GE Sanda
• Y Baumer
• Q Ng
• AK Dey
• HL Teague
• AV Sorokin
• PK Dakur
• JI Silverman
• CL Harrington
• JA Rodante
• DA Springer
• CK Bleck
• CL Thomas
• ZX Yu
• MC Winge
• HS Kruth
• MP Marinkovich
• AA Joshi
• MP Playford
• NN Mehta

Abstract

Psoriasis is a chronic inflammatory skin disease that is associated with increased cardiometabolic dysfunction however mechanistic links between the two diseases states remain understudied. Several psoriasis mouse models have been described in the past, failing to develop cardiometabolic dysfunction or atherosclerosis. In this study, we utilize the K14-Rac1V12 mouse model which due to keratinocyte-specific overexpression of active Rac1V12 presents clinically as psoriasis with important cardiometabolic features of the human disease such as dyslipidemia and pro-atherosclerotic macrophages. To study atherogenesis in the context of psoriasis-induced chronic inflammation we crossed the K14-RacV12+/- mouse into Srb-/-/ApoER61h/h, an aggressive, short term atherosclerosis mouse model. K14-RacV12+/-/Srb-/-/ApoER61h/h mice and their age and gender-matched Srb-/-/ApoER61h/h were put on high fat diet (HFD) for 2 weeks. Psoriasis severity was evaluated before the initiation of HFD and at time of sacrifice. A classical atherosclerosis study was performed. We found that upon HFD, psoriasis phenotype worsens, lymph node and spleen immune cell composition change while no differences in plasma lipid levels are observed. Importantly, aortas display a 6.8fold increase in atherosclerosis plaque formation as determined by Oil Red-O en face analysis. Aortic sinus sections confirmed these results (2.5fold increase) and display macrophage-rich plaques with a 2fold increased cholesterol crystal deposition and necrotic core area in K14-RacV12+/-/Srb-/-/ApoER61h/h mice compared to Srb-/-/ApoER61h/h. For the first time, a psoriatic mouse was successfully crossed into an atherosclerosis prone mouse model and thus, providing an innovative research tool to investigate, develop and test targeted therapies for both psoriasis-related atherogenesis

Scientific Focus Area: Immunology

This page was last updated on Friday, March 26, 2021