MYOCARDIAL FUNCTION AND FFA METABOLISM IN HIV-METABOLIC SYNDROME

HIV 代谢综合征中的心肌功能和 FFA 代谢

• 批准号: 7603362
• 负责人: KEVIN E YARASHESKI
• 金额: $ 2.08万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603362
• 关键词: Anti-Retroviral Agents; Appearance; Blood Circulation; Cardiac; Cardiovascular Diseases; Computer Retrieval of Information on Scientific Projects Database; Doppler Echocardiography; Dyslipidemias; Fatty Acids; Functional disorder; Funding; General Population; Grant; Heart; High Density Lipoprotein Cholesterol; Hypertriglyceridemia; Image; Institution; Insulin Resistance; Label; Left; Left Ventricular Dysfunction; Left ventricular structure; Link; Lipids; Liver; Mass Spectrum Analysis; Metabolic syndrome; Metabolism; Myocardial; Myocardium; Nonesterified Fatty Acids; Obesity; Palmitates; Pathogenesis; Positron-Emission Tomography; Radio; Rate; Reporting; Research; Research Personnel; Resources; Risk Factors; Skeletal Muscle; Source; Tissues; United States National Institutes of Health; Ventricular; Visceral; Woman; cardiovascular disorder risk; experience; men; oxidation; therapy design; uptake

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. The risk for cardiovascular disease (CVD) and left ventricular dysfunction (LVD) is greater in HIV-infected people than in the general population, but the pathogenesis is unclear. Many HIV-infected people develop metabolic syndromes (HIV+MS) that include traditional CVD and LVD risk factors (dyslipidemia, insulin resistance, visceral adiposity) that are commonly observed in HIV-seronegative people and referred to as "The Metabolic Syndrome." We have reported that HIV+MS is characterized by an elevated free fatty acid rate of appearance (FFA Ra) in the circulation (i.e., increased whole-body lipolytic rate), and lipid accumulation in skeletal muscle and liver. In HIV+MS, we hypothesize that the elevated FFA Ra increases FFA delivery, uptake and oxidation by the myocardium, but that myocardial FFA uptake eventually exceeds the ability of the heart to oxidize FFAs: intramyocardial lipid accumulation may result. We hypothesize that increased myocardial FFA uptake and oxidation are associated with structural changes in the left ventricle, and ventricular diastolic and systolic contractile dysfunction in HIV+MS. We propose to quantify whole-body FFA Ra (using 13C-palmitate and mass spectrometry), myocardial FFA delivery, uptake and oxidation (using radio-labeled palmitate and cardiac positron emission tomography (PET) imaging), and left ventricular (LV) structure, diastolic and systolic contractile function using 2-D and tissue Doppler echocardiography) in 30 HIV+MS and 30 HIV-infected people without MS. We will compare these parameters between these 2 groups, and to exactly the same parameters quantified in HIV-seronegative people with and without "The Metabolic Syndrome" who are currently being studied by co-investigators on this proposal at our Institution. For this project, HIV+MS is defined as HIV-infected women and men receiving stable anti-retroviral therapy and experiencing hypertriglyceridemia, low HDL-cholesterol levels, insulin resistance and visceral adiposity. The findings will identify similarities/differences in myocardial metabolism and LV contractile function between HIV+MS and "The Metabolic Syndrome." The findings may provide a mechanistic link between dysregulated whole-body and myocardial FFA metabolism that contributes to alterations in LV structure, contractile function and CVD. If so, treatments designed to reduce circulating FFA levels in HIV+MS, might effectively reduce CVD and LVD in HIV-infected people.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 HIV感染者患心血管疾病（CVD）和左心室功能障碍（LVD）的风险高于普通人群，但发病机制尚不清楚。 许多 HIV 感染者会出现代谢综合征 (HIV+MS)，其中包括传统的 CVD 和 LVD 危险因素（血脂异常、胰岛素抵抗、内脏肥胖），这些因素在 HIV 血清阴性人群中常见，被称为“代谢综合征”。 我们报道过，HIV+MS 的特征是循环中游离脂肪酸出现率 (FFA Ra) 升高（即全身脂肪分解率增加），以及骨骼肌和肝脏中脂质积累。 在 HIV+MS 中，我们假设升高的 FFA Ra 会增加心肌的 FFA 递送、摄取和氧化，但心肌 FFA 摄取最终超过心脏氧化 FFA 的能力：可能导致心肌内脂质积累。 我们假设心肌 FFA 摄取和氧化增加与 HIV+MS 中左心室的结构变化以及心室舒张和收缩功能障碍有关。 我们建议量化全身 FFA Ra（使用 13C-棕榈酸盐和质谱法）、心肌 FFA 输送、摄取和氧化（使用放射性标记的棕榈酸盐和心脏正电子发射断层扫描 (PET) 成像）以及左心室 (LV) 结构、舒张期和收缩期收缩功能（使用二维和组织多普勒超声心动图）对 30 名 HIV+MS 和 30 名 HIV 感染者（未进行 多发性硬化症。 我们将比较这两组之间的这些参数，并与患有和不患有“代谢综合症”的艾滋病毒血清阴性人群中量化的完全相同的参数进行比较，这些参数目前正在由我们机构的联合研究人员根据这项提案进行研究。 在该项目中，HIV+MS 被定义为接受稳定抗逆转录病毒治疗并出现高甘油三酯血症、低 HDL 胆固醇水平、胰岛素抵抗和内脏肥胖的 HIV 感染女性和男性。 研究结果将确定 HIV+MS 和“代谢综合征”之间心肌代谢和左心室收缩功能的相似/差异。 这些发现可能提供全身失调和心肌 FFA 代谢之间的机制联系，从而导致左心室结构、收缩功能和 CVD 的改变。 如果是这样，旨在降低 HIV+MS 患者循环 FFA 水平的治疗可能会有效减少 HIV 感染者的 CVD 和 LVD。