Pc4 PDT for Psoriasis

银屑病是一种常见的慢性免疫介导的疾病，影响约2%的美国人口， 以激活的免疫系统为特征。最近的回顾性研究表明， 银屑病患者患肥胖、糖尿病、高血压、高脂血症和心肌梗死的风险增加 梗塞我们假设银屑病患者心血管风险增加可能是由 牛皮癣的皮肤炎症。S100 A8/A9由活化的骨髓细胞合成，募集 他们的炎症环境，并可以作为未来心血管事件的预测。 S100 A8/A9在银屑病皮肤中的表皮和骨髓细胞中显著上调，并且S100 A8/A9的水平在银屑病皮肤中的表皮和骨髓细胞中显著上调。 银屑病组织和血清中S100 A8/A9与银屑病的严重程度相关。VEGF，另一种亲- 炎症标志物在银屑病和心血管疾病中也上调， 巨噬细胞反应，并似乎调节S100 A8/A9的表达。在积极治疗 银屑病患者VEGF和S100 A8/A9蛋白表达明显降低。我们建议皮肤驱动 由促炎性S100 A8/A9和VEGF水平升高所产生的炎症有助于 在银屑病中观察到的增加的心血管风险和用抗心血管疾病药物进行银屑病的积极全身治疗 有效的药物可以通过降低S100 A8/A9和VEGF的水平来降低心血管风险。我们 将确定：银屑病患者发展为心血管疾病的倾向;短期治疗的效果。 银屑病的长期全身治疗对血管功能障碍作为心血管疾病的指标 风险;和长期治疗银屑病的积极的系统性治疗的效果，旨在最大限度地提高 银屑病控制颈动脉内膜中层厚度作为心血管风险的指标。此外，血清 S100 A8/A9和VEGF水平以及其他潜在的炎症血清标志物，包括hsCRP， 将测量髓过氧化物酶、功能障碍的HDL和对氧磷酶。组织巨噬细胞将 基因组分析，试图将巨噬细胞活化与银屑病和心血管风险相关联。 我们的研究结果可能确定银屑病，炎症和心血管风险之间的第一个直接联系。

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.