Meta-inflammation in Psoriasis-associated Atherosclerosis

Psoriasis is a chronic heterogeneous inflammatory skin disease, affecting over 100 million people worldwide, for which there is no cure. However, disease manifestations are not limited to the skin. Psoriasis is associated with chronic inflammation, which spreads throughout the body and increases the risk of numerous comorbidities, including cardiovascular disease, type 2 diabetes, obesity, depression, and psoriatic arthritis. Atherosclerotic cardiovascular disease and its risk factors, e.g. metabolic syndrome, are associated with significantly increased mortality rates for patients with psoriasis. Although strong evidence for the association between psoriasis, atherosclerosis, and metabolic syndrome is provided by epidemiological studies, the mechanisms behind this association remain elusive. The project aims to investigate the complex interactions between the inflammatory environment and metabolism in psoriasis and atherosclerosis using Genetically Engineered Mouse Models (GEMMs), which are powerful tools to study multifactorial human diseases and to test new therapies. To address the key research questions, preclinical mouse models of psoriasis-like disease will be combined with experimental and genetic models of atherosclerosis. A multidisciplinary approach combining unbiased transcriptomic and proteomic analyses with biochemical, molecular, and microscopy methods will identify molecular and cellular mechanisms potentially linking psoriasis with atherosclerosis and metabolic syndrome. Analyses of serum samples from psoriasis patients will complement the project and further establish the relevance to human disease. Therefore, the project will provide insights into the complex functional crosstalk between the immune system and metabolism in psoriasis-associated atherosclerosis and metabolic syndrome. The results will have clinical implications and may lead to novel diagnostic and therapeutic strategies to improve the quality of life and reduce cardiovascular disease risk in psoriasis patients.