Adipose tissue underlying psoriasis plaques is the most accessible tissue to direct analysis for a reduction in co-morbidity pathophysiology. Interestingly, psoriasis lesion show altered expression of leptin receptors in the "skin" component18 but no studies have been done to compare "skin" vs. adipose tissue. We want to use powerful, high density, arrays and functional imaging studies to assess the degree of inflammation and associated metabolic derangement in fat tissue and then determine the extent to which a reduction in inflammatory circuits in the skin affects the core pathology in fat tissue. Associated biomarker and functional assessments of the cardiovascular tree will provide critical information on whether associated cardiovascular dysfunction can be reversed by treating inflammation in the primary site. If this study is successful, it will not only extend information on the pathophysiology of psoriasis and disease-specific co-morbid risks, but it will also provide guidance on whether long-term effective treatment of inflammation could improve long-term tissue outcomes deeper than the skin. Some of the studies we propose are "firsts" for the study of psoriasis and stand to create new research approaches for psoriasis and other diseases that have similar inflammatory and co-morbid risks. Preliminary Studies Studies in rheumatoid arthritis (RA) patients, another chronic inflammatory disease associated with increased risk for CVD, showed that response to methotrexate treatment is associated with reduction in CVD events and mortality. Biologic treatments for psoriasis, e.g. anti TNF-α (etanercept) or anti p-40 (ustekinumab), have also been shown to reduce C reactive protein (CRP) in short-term trials. A key hypothesis to this study is that the classical TNF pathway (TNF,IL-1,IL-6,IL-8 then the NF kappa B immediate genes) contributes directly to the metabolic alterations in psoriatic patients and that this pathway could also drive systemic inflammation. CRP is produced in the liver in response to IL-6. Many other inflammatory mediators associated with increased CVD risk are made at excess levels in psoriasis lesions and may well contribute to the systemic inflammation burden through release into the circulation. We have used gene arrays and RT-PCR to follow systemic modulation of these CVD related inflammatory molecules in previous studies and will extend this analysis to adipose tissue in this study. However, the question whether long-term effective management of psoriasis can alter the pathophysiology of its comorbid conditions has not been investigated yet.