Pc4 PDT for Psoriasis

Pc4 PDT 治疗银屑病

• 批准号: 7928964
• 负责人: ELMA D BARON
• 金额: $ 32.52万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7928964
• 关键词: Affect; Aftercare; Age; Autoimmune Diseases; Biological Assay; Biological Markers; Blood Vessels; C-reactive protein; Cardiovascular Diseases; Cardiovascular system; Carotid Arteries; Chronic; Dendritic Cells; Diabetes Mellitus; Disease; Endothelial Cells; Environment; Epidermis; Event; Functional disorder; Future; Genes; Genomics; High Density Lipoproteins; Hyperlipidemia; Hypertension; Immune; Immune system; Inflammation; Inflammatory; Interleukin-2; Link; Long-Term Effects; Lymphocyte; Macrophage Activation; Measures; Medial; Mediating; Mediator of activation protein; Myelogenous; Myeloid Cells; Myocardial Infarction; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Patients; Peroxidases; Population; Proteins; Psoriasis; RNA; Reaction; Recruitment Activity; Reporting; Research Personnel; Retrospective Studies; Role; Serum; Serum Markers; Severities; Skin; Surrogate Markers; Systemic Therapy; T-Lymphocyte; Thick; Tissues; Translational Research; United States; Vascular Endothelial Growth Factors; Work; aryldialkylphosphatase; brachial artery; cardiovascular risk factor; cytokine; inflammatory marker; keratinocyte; macrophage; novel; obesity risk; programs; protein expression

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.

牛皮癣是一种常见的慢性免疫介导性疾病，影响-2%的美国人口，是 以激活的免疫系统为特征的。最近的回顾研究表明，患者 患有银屑病的人患肥胖症、糖尿病、高血压、高脂血症和心肌梗塞的风险增加 脑梗塞。我们推测牛皮癣患者心血管风险的增加可能是由 牛皮癣中发生的皮肤炎。S100A8/A9由激活的髓系细胞合成，新兵 它们与炎症环境有关，并可作为未来心血管事件的预测因子。 S100A8/A9在银屑病患者皮肤、表皮和髓系细胞中显著上调，其水平 银屑病组织和血清中S100A8/A9与银屑病严重程度相关。另一位拥护者--血管内皮生长因子 炎症标记物在银屑病和心血管疾病中也上调，也可以诱发 巨噬细胞反应，并似乎调节S100A8/A9的表达。在积极治疗后 银屑病、血管内皮生长因子和S100A8/A9蛋白表达均显著降低。我们认为皮肤驱动 促炎症因子S100A8/A9和血管内皮生长因子水平升高引起的炎症 银屑病患者心血管风险增加，银屑病的积极系统治疗 强效药物可通过降低S100A8/A9和血管内皮生长因子水平来降低心血管风险。我们 将确定：银屑病患者患心血管疾病的倾向；短效 银屑病的长期治疗以血管功能障碍作为心血管指标的系统治疗 风险；以及长期治疗牛皮癣的效果，采用积极的系统疗法，旨在最大限度地 控制银屑病患者颈动脉内膜中层厚度作为心血管风险的指标。此外，血清 S100A8/A9和血管内皮生长因子水平以及其他潜在的血清炎症标志物，包括hsCRP， 将测定髓过氧化物酶、功能失调的高密度脂蛋白和对氧磷酶。组织巨噬细胞将是 基因组分析，以努力将巨噬细胞激活与牛皮癣和心血管疾病风险联系起来。 我们的发现可能确定牛皮癣、炎症和心血管风险之间的第一个直接联系。