Effect of Atorvastatin on Endothelial Function and Raynaud in Diffuse Scleroderma

阿托伐他汀对弥漫性硬皮病内皮功能和雷诺氏的影响

基本信息

批准号：
8832216
负责人：
Robyn Therese Domsic
金额：
$ 20.16万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-02-01 至 2017-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8832216
关键词：
Affect Age Autoimmune Diseases Autoimmune Process Blood Vessels Blood capillaries Cell Adhesion Molecules Clinical Clinical Trials Complex Complication Conflict (Psychology)Connective Tissue Diseases Cutaneous Data Diffuse Scleroderma Disease Disease Progression Early Diagnosis Early Intervention Early treatment Endothelial Cells Event FDA approved Fibrosis Fingers Functional disorder Gangrene Gender Image Imaging Techniques Immune system Immunologics Individual Injury Intervention Ischemia Lasers Lymphocyte Measurement Measures Mediating Microcirculation Microvascular Dysfunction Modality Nitric Oxide Oral Organ Outcome Pathogenesis Patients Pattern Pharmaceutical Preparations Pilot Projects Placebos Process Production Publishing Pulmonary Hypertension Race Raynaud Disease Reperfusion Therapy Risk Skin Surrogate Markers Symptoms Systemic Scleroderma Testing Toes Ulcer Vascular Diseases Work atorvastatin brachial artery capillary cell injury cohort contrast imaging design digital endothelial dysfunction experience imaging modality improved migration mortality novel therapeutics pleiotropism prevent public health relevance response targeted treatment theories vascular abnormality vascular smooth muscle cell proliferation

项目摘要

DESCRIPTION: Systemic sclerosis (SSc) is a multisystem autoimmune illness characterized by vasculopathy, immune system activation and fibrosis of the skin and internal organs. SSc affects approximately 240 people per million in the US, but is a disease for which there is no FDA approved medication. Current hypothesis of pathogenesis suggest that a vascular injury with endothelial dysfunction may be an inciting event contributing to immunologic activation and fibrosis in the pathogenesis of the disease. More than 90% of individuals with SSc have vascular complications including Raynaud phenomenon, digital ulcers or gangrene and pulmonary hypertension, with microvascular abnormalities felt to contribute to Raynaud and digital ulcerations. Statin medications are well-recognized to have pleiotropic effects which may modify all aspects of SSc pathogenesis. A few preliminary statin studies have found conflicting results, but have used patients with overall longstanding disease, when the vasculopathy may have not been amenable to treatment. In our preliminary work we have found evidence that statins may mediate microvascular endothelial dysfunction in patients with very early systemic sclerosis. Laser speckle contrast imaging (LSCI) is a newer imaging modality that assesses microcirculation and has been proposed as a surrogate marker for systemic microvascular function. Our preliminary data showed a distinct pattern of microcirculatory flow as measured by LSCI compared to healthy age, gender and race-matched controls and holds promise as a functional assessment of microvascular function in SSc patients. Our hypothesis are that treatment with atorvastatin in a well-defined cohort of early diffuse SSc will improve microvascular endothelial function as measured by EndoPAT and thereby improve related Raynaud symptoms. We propose to apply LSCI imaging as a modality to assess microvascular endothelial function response to statins and hypothesize that this modality will allow us to predict responders to statins.

描述：系统性硬化症（SSC）是一种多系统自身免疫性疾病，其特征是皮肤和内部器官的血管病，免疫系统激活和纤维化。在美国，SSC影响约240人，但没有FDA批准的药物。当前的发病机理假设表明，内皮功能障碍的血管损伤可能是煽动疾病发病机理的免疫激活和纤维化的煽动性事件。超过90％的SSC患者患有血管并发症，包括Raynaud现象，数字溃疡或坏疽和肺动脉高压，而微血管异常则有助于Raynaud和数字溃疡。他汀类药物被众所周知具有多效作用，可以改变SSC发病机理的所有方面。一些初步的他汀类药物研究发现了矛盾的结果，但使用了总体长期疾病的患者，而血管病可能无法接受治疗。在我们的初步工作中，我们发现了证据表明他汀类药物可以介导非常早期的系统性硬化症患者的微血管内皮功能障碍。激光斑点对比成像（LSCI）是一种较新的成像方式，可评估微循环，并已被提议作为全身微血管功能的替代标记。我们的初步数据显示，与健康年龄，性别和种族匹配的控制相比，LSCI测量的微循环流的明显模式，并保持了SSC患者微血管功能的功能评估。我们的假设是，用明确定义的早期弥漫性SSC进行治疗将改善通过内尾衡量的微血管内皮功能，从而改善相关的Raynaud符号。我们建议将LSCI成像作为一种方式，以评估对他汀类药物的微血管内皮功能反应，并假设这种方式将使我们能够预测他汀类药物的反应者。