THE RELATIONSHIP OF HEPATIC STEATOSIS TO ENDOTHELIAL DYSFUNCTION IN PATIENTS

患者肝脂肪变性与内皮功能障碍的关系

• 批准号: 8166578
• 负责人: RICHARD K. STERLING
• 金额: $ 0.29万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8166578
• 关键词: Age; Alcohol consumption; Atherosclerosis; Biological Markers; Blood Vessels; Body Composition; Cardiovascular Diseases; Cardiovascular system; Chemistry; Computer Retrieval of Information on Scientific Projects Database; DEXA; Databases; Diabetes Mellitus; Exclusion Criteria; Fasting; Fatty Liver; Fingers; Functional disorder; Funding; Future; Gender; Grant; HIV; HIV Infections; Hepatic; Hepatitis B; Hypertension; Inflammatory; Injury; Institution; Insulin Resistance; Laboratories; Lipids; Lipoxygenase; Liver diseases; Magnetic Resonance Spectroscopy; Metabolic; Metabolic syndrome; Patients; Physiologic pulse; Pilot Projects; Plasma; Race; Recording of previous events; Research; Research Personnel; Resources; Serum; Severities; Smoking History; Source; United States National Institutes of Health; antiretroviral therapy; cardiovascular risk factor; demographics; liver biopsy; meetings; non-alcoholic fatty liver

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In HIV infected subjects, the presence of NAFLD is associated with increased evidence of vascular injury and cardiovascular disease due to the systemic activation of lipoxygenase which in turn causes endothelial dysfunction and promotes atherosclerosis. The specific aims: 1. To define the impact of hepatic steatosis on the severity of endothelial injury and macrovascular cardiovascular status in subjects with HIV infection. 2. To assess, through lipidomic analysis, the relationship between endothelial dysfunction and hepatic steatosis in patients with HIV. In this pilot study, 10 HIV patients who had previously undergone liver biopsy for liver disease who have steatosis (>5%) and 10 matched by age (¿ 5 yrs), gender, and race without steatosis (<5%) will be selected from the data base (VCU IRB#6033). All subjects will meet inclusion/exclusion criteria. At baseline demographics, comorbid conditions (diabetes, hypertension, hepatitis B or C), antiretroviral therapy history, body composition (using anthropometrics and DEXA), presence of the metabolic syndrome (using ATPIII criteria), alcohol use (assessed by AUDIT), THC use, smoking history, and laboratories for CBC, CD4/CD8, HIV RNA, and serum chemistries (basic metabolic and hepatic panel) and fasting lipids. The primary endpoint is increased cIMT. Subjects will have endothelial dysfunction assessed by finger arterial pulse wave amplitude (EndoPAT) and Framingham score will be calculated for future cardiovascular risk. MR spectroscopy will be performed to assess for hepatic steatosis. Serum/plasma will be assessed for insulin resistance (HOMA-IR), inflammatory biomarkers, and lipidomic analysis.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在HIV感染的受试者中，NAFLD的存在与血管损伤和心血管疾病的证据增加有关，这是由于脂氧合酶的全身性激活，这反过来又引起内皮功能障碍并促进动脉粥样硬化。 具体目标： 1. 明确肝脂肪变性对HIV感染者内皮损伤严重程度和大血管心血管状态的影响。 2. 通过脂质组学分析评估HIV患者内皮功能障碍与肝脂肪变性之间的关系。 在这项初步研究中，将从数据库（VCU IRB#6033）中选择10名先前接受过肝脏疾病肝活检的患有脂肪变性（>5%）的HIV患者和10名年龄（~ 5岁）、性别和种族匹配但没有脂肪变性（<5%）的HIV患者。 所有受试者均符合入选/排除标准。 基线人口统计学、共病（糖尿病、高血压、B或C型肝炎）、抗逆转录病毒治疗史、身体组成（使用人体测量学和DEXA）、代谢综合征的存在（使用ATP III标准）、饮酒（通过AUDIT评估）、THC使用、吸烟史、CBC、CD 4/CD 8、HIV RNA和血清化学（基础代谢和肝脏检查）和空腹血脂实验室检查。 主要终点是cIMT增加。 将通过手指动脉脉搏波振幅（EndoPAT）评估受试者的内皮功能障碍，并计算未来心血管风险的Fragrance评分。 将进行MR光谱检查以评估肝脏脂肪变性。 将评估血清/血浆的胰岛素抵抗（HOMA-IR）、炎症生物标志物和脂质组学分析。