Pc4 PDT for Psoriasis

Pc4 PDT 治疗银屑病

• 批准号: 8319617
• 负责人: ELMA D BARON
• 金额: $ 21.58万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8319617
• 关键词: Affect; Autoimmune Diseases; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Chronic; Dendritic Cells; Diabetes Mellitus; Disease; Environment; Epidermis; Event; Functional disorder; Future; High Density Lipoproteins; Hyperlipidemia; Hypertension; Immune; Immune system; Inflammation; Inflammatory; Interleukin-2; Link; Long-Term Effects; Lymphocyte; Macrophage Activation; Measures; Medial; Mediating; Myelogenous; Myeloid Cells; Myocardial Infarction; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Patients; Peroxidases; Population; Proteins; Psoriasis; Reaction; Recruitment Activity; Reporting; Retrospective Studies; Role; S100A8 gene; Serum; Serum Markers; Severities; Skin; Systemic Therapy; T-Lymphocyte; Thick; Tissues; Translational Research; United States; Vascular Endothelial Growth Factors; aryldialkylphosphatase; cardiovascular risk factor; cytokine; inflammatory marker; keratinocyte; macrophage; obesity risk; 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疾病，影响 -2% 的美国人口，并且 其特征是免疫系统被激活。最近的回顾性研究表明，患者 患有牛皮癣的人患肥胖、糖尿病、高血压、高脂血症和心肌梗塞的风险增加 梗塞。我们假设银屑病导致的心血管风险增加可能是由于 牛皮癣发生的皮肤炎症。 S100A8/A9由活化的骨髓细胞合成，招募 它们可以将它们引入炎症环境，并可以作为未来心血管事件的预测因子。 S100A8/A9 在银屑病皮肤的表皮和骨髓细胞中显着上调，并且 银屑病组织和血清中的 S100A8/A9 与银屑病的严重程度相关。 VEGF，另一种亲 炎症标志物在牛皮癣和心血管疾病中也会上调，并且还可以引起 巨噬细胞反应，似乎调节 S100A8/A9 表达。积极治疗后 银屑病时，VEGF和S100A8/A9蛋白表达显着降低。我们建议皮肤驱动 促炎性 S100A8/A9 和 VEGF 水平升高产生的炎症有助于 银屑病心血管风险增加，积极全身治疗银屑病 有效的药物可以通过降低 S100A8/A9 和 VEGF 的水平来降低心血管风险。我们 将确定： 牛皮癣患者患心血管疾病的倾向；短的效果 通过以血管功能障碍为心血管指标的全身疗法来治疗牛皮癣 风险;以及采用积极的全身疗法长期治疗牛皮癣的效果，旨在最大限度地发挥作用 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 S100A8/A9 和 VEGF 的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、功能失调的高密度脂蛋白和对氧磷酶。组织巨噬细胞将 对巨噬细胞激活与牛皮癣和心血管风险进行基因组分析。 我们的研究结果可能首次确定了牛皮癣、炎症和心血管风险之间的直接联系。