Psoriasis is a common chronic immune mediated disease affecting -2% of the US population and is characterized by an activated immune system. Recent retrospective studies have demonstrated that patients with psoriasis have an increased risk of obesity, diabetes, hypertension, hyperlipidemia and myocardial infarction. We hypothesize that the increased cardiovascular risk that occurs in psoriasis may be driven by the skin inflammation that occurs in psoriasis. S100A8/A9 is synthesized by activated myeloid cells, recruits them to inflammatory environments, and can serve as a predictor of future cardiovascular events. S100A8/A9 is significantly upregulated in psoriatic skin in the epidermis and in myeloid cells and levels of S100A8/A9 in psoriatic tissue and serum correlate with severity of psoriasis. VEGF, another pro- inflammatory marker is also upregulated in both psoriasis and in cardiovascular disease and can also elicit macrophage reactions, and appears to regulate S100A8/A9 expression. Following aggressive treatment of psoriasis, VEGF and S100A8/A9 protein expression are significantly reduced. We propose that skin driven inflammation generated by elevated levels of proinflammatory S100A8/A9 and VEGF contribute to the increased cardiovascular risk seen in psoriasis and that aggressive systemic treatment of psoriasis with potent agents can drive down the cardiovascular risk by decreasing the levels of S100A8/A9 and VEGF. We will determine: the propensity of patients with psoriasis to develop cardiovascular disease;the effect of short term treatment of psoriasis with systemic therapies on vascular dysfunction as an indicator of cardiovascular risk;and the effect of long term treatment of psoriasis with aggressive systemic therapies aimed to maximize psoriasis control on carotid intimal medial thickness as an indicator of cardiovascular risk. In addition, serum levels of S100A8/A9 and VEGF as well as other potential serum markers of inflammation, including hsCRP, myeloperoxidase, dysfunctional HDL and paraoxonase will be measured. Tissues macrophages will be genomically profiled in an effort to correlate macrophage activation with psoriasis and cardiovascular risk. Our findings may identify the first direct link between psoriasis, inflammation and cardiovascular risk.
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